.. .. ,

.. .. ,

.. .. ,

.. .. ,

.. .. ,

.. .. Le,

.. .. Le-cancer-du-poumon,

.. .. Le,

S. Chatterjee, L. Crozet, D. Damotte, K. Iribarren, C. Schramm et al., TLR7 promotes tumor progression, chemotherapy resistance, and poor clinical outcomes in nonsmall cell lung cancer, Cancer Res, vol.74, issue.18, pp.5008-5026, 2014.

P. Serafini, R. Carbley, K. A. Noonan, and G. Tan,

E. Chun, S. Lavoie, M. Michaud, C. A. Gallini, J. Kim et al., CCL2 Promotes Colorectal Carcinogenesis by Enhancing Polymorphonuclear Myeloid-Derived Suppressor Cell Population and Function. Cell Rep, vol.12, pp.244-57, 2015.

Z. Li, S. Ye, L. Ouyang, H. Zhang, Y. Chen et al., COX-2 promotes suppressor cells, Oncoimmunology, vol.4, issue.11, p.1044712, 2015.

A. S. Pak, M. A. Wright, J. P. Matthews, S. L. Collins, G. J. Petruzzelli et al.,

V. Bronte, D. B. Chappell, E. Apolloni, A. Cabrelle, M. Wang et al.,

P. Filipazzi, R. Valenti, V. Huber, L. Pilla, P. Canese et al.,

, J Clin Oncol Off J Am Soc Clin Oncol, vol.25, issue.18, pp.2546-53, 2007.

S. K. Bunt, L. Yang, P. Sinha, V. K. Clements, J. Leips et al., Reduced limits tumor progression. Cancer Res, vol.67, pp.10019-10045, 2007.

Z. G. Fridlender, G. Buchlis, V. Kapoor, G. Cheng, J. Sun et al., CCL2 blockade augments cancer immunotherapy, Cancer Res, vol.70, issue.1, pp.109-127, 2010.

D. Gabrilovich, Mechanisms and functional significance of tumour-induced dendritic

D. Sanctis, F. Solito, S. Ugel, S. Molon, B. Bronte et al., MDSCs in cancer: Conceiving new prognostic and therapeutic targets, Biochim Biophys Acta, 2016.

T. Kitamura, B. Qian, and J. W. Pollard, Immune cell promotion of metastasis, Nat Rev Immunol, vol.15, issue.2, pp.73-86, 2015.

M. C. Schmid and J. A. Varner, Myeloid cells in the tumor microenvironment: modulation of tumor angiogenesis and tumor inflammation, J Oncol, p.201026, 2010.

M. K. Srivastava, L. Zhu, M. Harris-white, U. K. Kar, U. Kar et al.,

M. J. Hendrix, E. A. Seftor, Y. W. Chu, K. T. Trevor, and R. E. Seftor, Role of intermediate filaments in migration, invasion and metastasis, Cancer Metastasis Rev, vol.15, issue.4, pp.507-532, 1996.

A. M. Szász, A. Lánczky, Á. Nagy, S. Förster, K. Hark et al.,

F. C. Detterbeck, D. J. Boffa, and L. T. Tanoue, The new lung cancer staging system

E. Brambilla, W. D. Travis, T. V. Colby, B. Corrin, and Y. Shimosato, The new World Health Organization classification of lung tumours, Eur Respir J, vol.18, issue.6, pp.1059-68, 2001.

F. Abe, A. J. Dafferner, M. Donkor, S. N. Westphal, E. M. Scholar et al., Myeloid-derived suppressor cells in mammary tumor progression in FVB Neu transgenic mice, Cancer Immunol. Immunother. CII, vol.59, p.47, 2010.

K. Adachi and K. Tamada, , 2015.

S. Adams, Toll-like receptor agonists in cancer therapy, Immunotherapy, vol.1, pp.949-964, 2009.

S. Adams, D. W. O'neill, D. Nonaka, E. Hardin, L. Chiriboga et al., Immunization of malignant melanoma patients with full-length NY-ESO-1 protein using TLR7 agonist imiquimod as vaccine adjuvant, J. Immunol. Baltim. Md, vol.181, pp.776-784, 1950.

B. B. Aggarwal, R. V. Vijayalekshmi, and B. Sung, Targeting inflammatory pathways for prevention and therapy of cancer: short-term friend, long-term foe, Clin. Cancer Res. Off, 2009.

, J. Am. Assoc. Cancer Res, vol.15, pp.425-430

A. Ahmed, J. H. Wang, and H. P. Redmond, , 2013.

S. Akira, K. Takeda, and T. Kaisho, Toll-like receptors: critical proteins linking innate and acquired immunity, Nat. Immunol, vol.2, pp.675-680, 2001.

S. Akira, S. Uematsu, and O. Takeuchi, Pathogen recognition and innate immunity, Cell, vol.124, pp.783-801, 2006.

L. Alexopoulou, A. C. Holt, R. Medzhitov, and R. A. Flavell, Recognition of doublestranded RNA and activation of NF-kappaB by Toll-like receptor 3, Nature, vol.413, pp.732-738, 2001.

A. O. Aliprantis, R. B. Yang, M. R. Mark, S. Suggett, B. Devaux et al., Cell activation and apoptosis by bacterial lipoproteins through toll-like receptor-2, Science, vol.285, pp.736-739, 1999.

K. I. Al-shibli, T. Donnem, S. Al-saad, M. Persson, R. M. Bremnes et al.,

, Prognostic effect of epithelial and stromal lymphocyte infiltration in non-small cell lung cancer, Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res, vol.14, pp.5220-5227

I. Angulo, J. Rullas, J. A. Campillo, E. Obregón, A. Heath et al., Early myeloid cells are high producers of nitric oxide upon CD40 plus IFN-gamma stimulation through a mechanism dependent on endogenous TNFalpha and IL-1alpha, Eur. J. Immunol, vol.30, pp.1263-1271, 2000.

A. Asea, Heat shock proteins and toll-like receptors, Handb. Exp. Pharmacol, pp.111-127, 2008.

C. Aspord, A. Pedroza-gonzalez, M. Gallegos, S. Tindle, E. C. Burton et al., Exp. Med, vol.204, pp.1037-1047, 2007.

C. Aspord, L. Tramcourt, C. Leloup, J. Molens, M. Leccia et al., Imiquimod inhibits melanoma development by promoting pDC cytotoxic functions and impeding tumor vascularization, J. Invest. Dermatol, vol.134, pp.2551-2561, 2014.

C. Badoual, S. Hans, J. Rodriguez, S. Peyrard, C. Klein et al., Prognostic value of tumorinfiltrating CD4+ T-cell subpopulations in head and neck cancers, Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res, vol.12, pp.465-472, 2006.

G. C. Bagby, C. A. Dinarello, P. Wallace, C. Wagner, S. Hefeneider et al., , 1986.

, Interleukin 1 stimulates granulocyte macrophage colony-stimulating activity release by vascular endothelial cells, J. Clin. Invest, vol.78, pp.1316-1323

J. Banchereau and R. M. Steinman, Dendritic cells and the control of immunity, Nature, vol.392, pp.245-252, 1998.

S. Basith, B. Manavalan, T. H. Yoo, S. G. Kim, and S. Choi, Roles of toll-like receptors in cancer: a double-edged sword for defense and offense, Arch. Pharm. Res, vol.35, pp.1297-1316, 2012.

A. K. Bauer, D. Dixon, L. M. Degraff, H. Cho, C. R. Walker et al., Toll-like receptor 4 in butylated hydroxytoluene-induced mouse pulmonary inflammation and tumorigenesis, J. Natl. Cancer Inst, vol.97, pp.1778-1781, 2005.

L. J. Bayne, G. L. Beatty, N. Jhala, C. E. Clark, A. D. Rhim et al., Tumor-derived granulocyte-macrophage colony-stimulating factor regulates myeloid inflammation and T cell immunity in pancreatic cancer, Cancer Cell, vol.21, pp.822-835, 2012.

R. P. Beasley, L. Y. Hwang, C. C. Lin, and C. S. Chien, Hepatocellular carcinoma and hepatitis B virus. A prospective study of 22 707 men in Taiwan, Lancet Lond. Engl, vol.2, pp.1129-1133, 1981.

E. Becht, N. A. Giraldo, C. Germain, A. De-reyniès, P. Laurent-puig et al., Immune Contexture, Immunoscore, and Malignant Cell Molecular Subgroups for Prognostic and Theranostic Classifications of Cancers, Adv. Immunol, vol.130, pp.95-190, 2016.

A. A. Beg, Endogenous ligands of Toll-like receptors: implications for regulating inflammatory and immune responses, Trends Immunol, vol.23, pp.509-512, 2002.

A. Beignon, K. Mckenna, M. Skoberne, O. Manches, I. Dasilva et al., Endocytosis of HIV-1 activates plasmacytoid dendritic cells via Toll-like receptor-viral RNA interactions, J. Clin. Invest, vol.115, pp.3265-3275, 2005.

R. Berger, H. Fiegl, G. Goebel, P. Obexer, M. Ausserlechner et al., , vol.101, pp.1059-1066, 2010.

J. J. Bernard, C. Cowing-zitron, T. Nakatsuji, B. Muehleisen, J. Muto et al., Ultraviolet radiation damages self noncoding RNA and is detected by TLR3, Nat. Med, vol.18, pp.1286-1290, 2012.

J. Berntsson, B. Nodin, J. Eberhard, P. Micke, J. et al., Prognostic impact of tumour-infiltrating B cells and plasma cells in colorectal cancer, Int. J. Cancer, vol.139, pp.1129-1139, 2016.

D. W. Beury, K. A. Carter, C. Nelson, P. Sinha, E. Hanson et al., Myeloid-Derived Suppressor Cell Survival and Function Are Regulated by the Transcription Factor Nrf2, J. Immunol. Baltim. Md, pp.3470-3478, 2016.

B. Beutler, Tlr4: central component of the sole mammalian LPS sensor, Curr. Opin. Immunol, vol.12, pp.20-26, 2000.

S. K. Biswas, L. Gangi, S. Paul, T. Schioppa, A. Saccani et al., A distinct and unique transcriptional program expressed by tumor-associated macrophages (defective NF-kappaB and enhanced IRF, 2006.

, /STAT1 activation), Blood, vol.107, pp.2112-2122

A. Boire, L. Covic, A. Agarwal, S. Jacques, S. Sherifi et al., , 2005.

R. Bonecchi, G. Bianchi, P. P. Bordignon, D. D'ambrosio, R. Lang et al., , 1998.

M. Boshart, L. Gissmann, H. Ikenberg, A. Kleinheinz, W. Scheurlen et al.,

A. Bowie and L. A. Neill, The interleukin-1 receptor/Toll-like receptor superfamily: signal generators for pro-inflammatory interleukins and microbial products, J. Leukoc. Biol, vol.67, pp.508-514, 2000.

J. R. Brahmer, C. G. Drake, I. Wollner, J. D. Powderly, J. Picus et al., Phase I study of singleagent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates, J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol, vol.28, pp.3167-3175, 2010.

M. S. Brault, K. , and R. A. , Impact of Tumor-Derived CCL2 on Macrophage Effector Function, J. Biomed. Biotechnol, pp.37-43, 2005.

H. D. Brightbill, D. H. Libraty, S. R. Krutzik, R. B. Yang, J. T. Belisle et al., Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors, Science, vol.285, pp.732-736, 1999.

C. Brignole, D. Marimpietri, D. Di-paolo, P. Perri, F. Morandi et al., Therapeutic targeting of TLR9 inhibits cell growth and induces apoptosis in neuroblastoma, Cancer Res, vol.70, pp.9816-9826, 2010.

C. Brito, M. Naviliat, A. C. Tiscornia, F. Vuillier, G. Gualco et al., Peroxynitrite inhibits T lymphocyte activation and proliferation by promoting impairment of tyrosine phosphorylation and peroxynitrite-driven apoptotic death, 1999.

, J. Immunol. Baltim. Md, vol.162, pp.3356-3366, 1950.

V. Bronte, M. Wang, W. W. Overwijk, D. R. Surman, F. Pericle et al., Apoptotic death of CD8+ T lymphocytes after immunization: induction of a suppressive population of Mac-1+/Gr-1+ cells, J. Immunol. Baltim. Md, vol.161, pp.5313-5320, 1950.

V. Bronte, D. B. Chappell, E. Apolloni, A. Cabrelle, M. Wang et al.,

, Unopposed production of granulocyte-macrophage colony-stimulating factor by tumors inhibits CD8+ T cell responses by dysregulating antigen-presenting cell maturation, J. Immunol. Baltim. Md, vol.162, pp.5728-5737, 1950.

V. Bronte, E. Apolloni, A. Cabrelle, R. Ronca, P. Serafini et al., , 2000.

V. Bronte, P. Serafini, C. De-santo, I. Marigo, V. Tosello et al., IL-4-induced arginase 1 suppresses alloreactive T cells in tumor-bearing mice, J. Immunol. Baltim. Md, vol.170, pp.270-278, 1950.

V. Bronte, S. Brandau, S. Chen, M. P. Colombo, A. B. Frey et al., Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards, Nat. Commun, vol.7, p.12150, 2016.

S. K. Bunt, P. Sinha, V. K. Clements, J. Leips, and S. Ostrand-rosenberg, Inflammation induces myeloid-derived suppressor cells that facilitate tumor progression, J. Immunol. Baltim. Md, vol.176, pp.284-290, 1950.

S. K. Bunt, V. K. Clements, E. M. Hanson, P. Sinha, and S. Ostrand-rosenberg, , 2009.

L. G. Burdelya, A. S. Gleiberman, I. Toshkov, S. Aygun-sunar, M. Bapardekar et al.,

, Toll-like receptor 5 agonist protects mice from dermatitis and oral mucositis caused by local radiation: implications for head-and-neck cancer radiotherapy, Int. J. Radiat. Oncol. Biol. Phys, vol.83, pp.228-234

R. Butsch, S. Lukas-waelti, S. Schaerer, J. Braun, D. Korol et al., Intratumoral plasmacytoid dendritic cells associate with increased survival in patients with follicular lymphoma, Leuk. Lymphoma, vol.52, pp.1230-1238, 2011.

C. Butts, A. Maksymiuk, G. Goss, D. Soulières, E. Marshall et al., Updated survival analysis in patients with stage IIIB or IV non-small-cell lung cancer receiving BLP25 liposome vaccine (L-BLP25): phase IIB randomized, multicenter, open-label trial, J. Cancer Res. Clin. Oncol, vol.137, pp.1337-1342, 2011.

C. Butts, M. A. Socinski, P. L. Mitchell, N. Thatcher, L. Havel et al., Tecemotide (L-BLP25) versus placebo after chemoradiotherapy for stage III non-small-cell lung cancer (START): a randomised, double-blind, Lancet Oncol, vol.15, pp.59-68, 2014.

Z. Cai, A. Sanchez, Z. Shi, T. Zhang, M. Liu et al., Activation of TollRes, vol.71, pp.2466-2475, 2011.

R. Cammarota, V. Bertolini, G. Pennesi, E. O. Bucci, O. Gottardi et al., The tumor microenvironment of colorectal cancer: stromal TLR-4 expression as a potential prognostic marker, J. Transl. Med, vol.8, 2010.

F. Chalmin, S. Ladoire, G. Mignot, J. Vincent, M. Bruchard et al., Membrane-associated Hsp72 from tumor-derived exosomes mediates STAT3-dependent immunosuppressive function of mouse and human myeloid-derived suppressor cells, J. Clin. Invest, vol.120, pp.457-471, 2010.
URL : https://hal.archives-ouvertes.fr/inserm-00451697

S. H. Chang, S. G. Mirabolfathinejad, H. Katta, A. M. Cumpian, L. Gong et al., T helper 17 cells play a critical pathogenic role in lung cancer, Proc. Natl. Acad. Sci. U. S. A, vol.111, pp.5664-5669, 2014.

Y. Chang, E. Cesarman, M. S. Pessin, F. Lee, J. Culpepper et al., Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma, Science, vol.266, pp.1865-1869, 1994.

S. Chatterjee, L. Crozet, D. Damotte, K. Iribarren, C. Schramm et al., TLR7 promotes tumor progression, chemotherapy resistance, and poor clinical outcomes in non-small cell lung cancer, Cancer Res, vol.74, pp.5008-5018, 2014.

W. Chen, Z. Li, L. Bai, L. , and Y. , NF-kappaB in lung cancer, a carcinogenesis mediator and a prevention and therapy target, Front. Biosci. Landmark Ed, vol.16, pp.1172-1185, 2011.

X. Chen, J. Wan, J. Liu, W. Xie, X. Diao et al., Increased IL-17-producing cells correlate with poor survival and lymphangiogenesis in NSCLC patients, Lung Cancer Amst. Neth, vol.69, pp.348-354, 2010.

X. Chen, F. Zhao, H. Zhang, Y. Zhu, K. Wu et al., Significance of TLR4/MyD88 expression in breast cancer, Int. J. Clin. Exp. Pathol, vol.8, pp.7034-7039, 2015.

Y. Chen, C. Mu, and J. Huang, , 2012.

J. Cherfils-vicini, S. Platonova, M. Gillard, L. Laurans, P. Validire et al., , 2010.

, J. Clin. Invest, vol.120, pp.1285-1297

V. Chew, C. Tow, C. Huang, E. Bard-chapeau, N. G. Copeland et al., Toll-like receptor 3 expressing tumor parenchyma and infiltrating natural killer cells in hepatocellular carcinoma patients, J. Natl. Cancer Inst, vol.104, pp.1796-1807, 2012.

M. R. Chicoine, M. Zahner, E. K. Won, R. R. Kalra, T. Kitamura et al., , 2007.

Q. L. Choo, G. Kuo, A. J. Weiner, L. R. Overby, D. W. Bradley et al., Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome, Science, vol.244, pp.359-362, 1989.

S. C. Chow, S. D. Gowing, J. J. Cools-lartigue, C. B. Chen, J. Berube et al., Int. J. Cancer, vol.136, pp.1341-1350, 2015.

E. Chun, S. Lavoie, M. Michaud, C. A. Gallini, J. Kim et al., CCL2 Promotes Colorectal Carcinogenesis by Enhancing Polymorphonuclear Myeloid-Derived Suppressor Cell Population and Function, Cell Rep, vol.12, pp.244-257, 2015.

K. F. Chung, Inflammatory mediators in chronic obstructive pulmonary disease, Curr. Drug Targets Inflamm. Allergy, vol.4, pp.619-625, 2005.

A. Churg, J. Dai, H. Tai, C. Xie, and J. L. Wright, Tumor necrosis factor-alpha is central to acute cigarette smoke-induced inflammation and connective tissue breakdown, 2002.

J. Respir, Crit. Care Med, vol.166, pp.849-854

P. C. Cogswell, D. C. Guttridge, W. K. Funkhouser, and A. S. Baldwin, Selective activation of NF-kappa B subunits in human breast cancer: potential roles for NF-kappa B2/p52 and for Bcl-3, Oncogene, vol.19, pp.1123-1131, 2000.

T. Condamine, I. Ramachandran, J. Youn, and D. I. Gabrilovich, Regulation of Tumor Metastasis by Myeloid-derived Suppressor Cells, Annu. Rev. Med, vol.66, pp.97-110, 2015.

J. Condeelis and J. W. Pollard, Macrophages: obligate partners for tumor cell migration, invasion, and metastasis, Cell, vol.124, pp.263-266, 2006.

C. Conrad, J. Gregorio, Y. Wang, T. Ito, S. Meller et al., , 2012.

W. A. Cooper, T. Tran, R. E. Vilain, J. Madore, C. I. Selinger et al., PD-L1 expression is a favorable prognostic factor in early stage non-small cell carcinoma, Lung Cancer Amst. Neth, vol.89, p.181, 2015.

L. M. Coussens and Z. Werb, Inflammation and cancer, Nature, vol.420, pp.860-867, 2002.

L. M. Coussens, C. L. Tinkle, D. Hanahan, and Z. Werb, MMP-9 supplied by bone marrow-derived cells contributes to skin carcinogenesis, Cell, vol.103, pp.481-490, 2000.

C. D'agostini, F. Pica, G. Febbraro, S. Grelli, C. Chiavaroli et al., , 2005.

, Antitumour effect of OM-174 and cyclophosphamide on murine B16 melanoma in different experimental conditions, Int. Immunopharmacol, vol.5, pp.1205-1212

M. Dajon, K. Iribarren, and I. Cremer, Toll-like receptor stimulation in cancer: A pro-and anti-tumor double-edged sword, 2016.

D. S. Dane, C. H. Cameron, and M. Briggs, Virus-like particles in serum of patients with Australia-antigen-associated hepatitis, Lancet Lond. Engl, vol.1, pp.695-698, 1970.

D. H. Dapito, A. Mencin, G. Gwak, J. Pradere, M. Jang et al., Promotion of hepatocellular carcinoma by the intestinal microbiota and TLR4, Cancer Cell, vol.21, pp.504-516, 2012.

M. De-cesare, C. Calcaterra, G. Pratesi, L. Gatti, F. Zunino et al., Eradication of ovarian tumor xenografts by locoregional administration of targeted immunotherapy, Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res, vol.14, pp.5512-5518, 2008.

F. De-sanctis, S. Solito, S. Ugel, B. Molon, V. Bronte et al., MDSCs in cancer: Conceiving new prognostic and therapeutic targets, Biochim. Biophys. Acta, vol.1865, pp.35-48, 2016.

D. G. Denardo, J. B. Barreto, P. Andreu, L. Vasquez, D. Tawfik et al., , 2009.

D. Giacomo, A. M. Biagioli, M. Maio, and M. , The emerging toxicity profiles of anti-CTLA-4 antibodies across clinical indications, Semin. Oncol, vol.37, pp.499-507, 2010.

D. Geng, S. Kaczanowska, A. Tsai, K. Younger, A. Ochoa et al., TLR5 Ligand-Secreting T Cells Reshape the Tumor Microenvironment and Enhance Antitumor Activity, vol.75, pp.1959-1971, 2015.

C. Germain, S. Gnjatic, F. Tamzalit, S. Knockaert, R. Remark et al., , 2014.

J. A. Gershan, K. M. Barr, J. J. Weber, W. Jing, J. et al., , 2015.

R. Ghittoni, R. Accardi, U. Hasan, T. Gheit, B. Sylla et al., The biological properties of E6 and E7 oncoproteins from human papillomaviruses, Virus Genes, vol.40, pp.1-13, 2010.

T. D. Gilmore, The Re1/NF-kappa B/I kappa B signal transduction pathway and cancer, Cancer Treat. Res, vol.115, pp.241-265, 2003.

J. Goc, C. Germain, T. K. Vo-bourgais, A. Lupo, C. Klein et al., , 2014.

P. Goldstraw, J. Crowley, K. Chansky, D. J. Giroux, P. A. Groome et al., The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours, J. Thorac. Oncol. Off. Publ. Int. Assoc. Study Lung Cancer, vol.2, pp.706-714, 2007.

D. Golgher, E. Jones, F. Powrie, T. Elliott, and A. Gallimore, , 2002.

J. Gomez-cambronero, J. Horn, C. C. Paul, and M. A. Baumann, Granulocytemacrophage colony-stimulating factor is a chemoattractant cytokine for human neutrophils: involvement of the ribosomal p70 S6 kinase signaling pathway, J. Immunol. Baltim. Md, vol.171, pp.6846-6855, 1950.

S. González-reyes, J. M. Fernández, L. O. González, A. Aguirre, A. Suárez et al., Study of TLR3, TLR4, and TLR9 in prostate carcinomas and their association with biochemical recurrence, Cancer Immunol. Immunother. CII, vol.60, pp.217-226, 2011.

J. A. Gonzalo, Y. Pan, C. M. Lloyd, G. Q. Jia, G. Yu et al., Mouse monocyte-derived chemokine is involved in airway hyperreactivity and lung inflammation, J. Immunol. Baltim. Md, vol.163, p.403, 1950.

E. Gorelik, R. H. Wiltrout, K. Okumura, S. Habu, and R. B. Herberman, Role of NK cells in the control of metastatic spread and growth of tumor cells in mice, Int. J. Cancer, vol.30, pp.107-112, 1982.

Y. Goto, T. Arigami, M. Kitago, S. L. Nguyen, N. Narita et al., Activation of Toll-like receptors 2, 3, and 4 on human melanoma cells induces inflammatory factors, Mol. Cancer Ther, vol.7, pp.3642-3653, 2008.

M. Grimm, M. Kim, A. Rosenwald, U. Heemann, C. Germer et al., Toll-like receptor (TLR) 7 and TLR8 expression on CD133+ cells in colorectal cancer points to a specific role for inflammation-induced TLRs in tumourigenesis and tumour progression, Eur. J. Cancer Oxf. Engl, vol.46, pp.2849-2857, 1990.

T. Grimmig, N. Matthes, K. Hoeland, S. Tripathi, A. Chandraker et al., TLR7 and TLR8 expression increases tumor cell proliferation and promotes chemoresistance in human pancreatic cancer, Int. J. Oncol, vol.47, pp.857-866, 2015.

S. I. Grivennikov, F. R. Greten, K. , and M. , Immunity, inflammation, and cancer. Cell, vol.140, pp.883-899, 2010.

J. Gu, R. Sun, S. Shen, Y. , and Z. , , pp.2215-2225, 2015.

C. Guido, D. Whitaker-menezes, C. Capparelli, R. Balliet, Z. Lin et al., Metabolic reprogramming of cancer-associated fibroblasts by TGF-? drives tumor growth: connecting TGF-? signaling with "Warburg-like" cancer metabolism and L-lactate production, Cell Cycle Georget. Tex, vol.11, pp.3019-3035, 2012.

C. Guiducci, M. Gong, A. Cepika, Z. Xu, C. Tripodo et al., RNA recognition by human TLR8 can lead to autoimmune inflammation, J. Exp. Med, vol.210, pp.2903-2919, 2013.

A. Haegens, . Van-der, A. Vliet, K. J. Butnor, N. Heintz et al., , 2005.

M. Hale, F. Itani, C. M. Buchta, G. Wald, M. Bing et al., Obesity triggers enhanced MDSC accumulation in murine renal tumors via elevated local production of CCL2, PloS One, vol.10, 2015.

L. S. Hammes, R. R. Tekmal, P. Naud, M. I. Edelweiss, N. Kirma et al., Macrophages, inflammation and risk of cervical intraepithelial neoplasia (CIN) progression--clinicopathological correlation, Gynecol. Oncol, vol.105, pp.157-165, 2007.

D. Hanahan and R. A. Weinberg, The hallmarks of cancer, Cell, vol.100, pp.57-70, 2000.

D. Hanahan and R. A. Weinberg, Hallmarks of cancer: the next generation, Cell, vol.144, pp.646-674, 2011.

M. Hausmann, S. Kiessling, S. Mestermann, G. Webb, T. Spöttl et al., Toll-like receptors 2 and 4 are up-regulated during intestinal inflammation, Gastroenterology, vol.122, 1987.

F. Hayashi, K. D. Smith, A. Ozinsky, T. R. Hawn, E. C. Yi et al., The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5, Nature, vol.410, pp.1099-1103, 2001.

W. He, Q. Liu, L. Wang, W. Chen, N. Li et al., Immunol, vol.44, pp.2850-2859, 2007.

F. Heil, H. Hemmi, H. Hochrein, F. Ampenberger, C. Kirschning et al., , vol.303, pp.1526-1529, 2004.

C. Helicobacter and . Collaborative-group, Gastric cancer and Helicobacter pylori, 2001.

H. Hemmi, O. Takeuchi, T. Kawai, T. Kaisho, S. Sato et al., A Toll-like receptor recognizes bacterial DNA, Nature, vol.408, pp.740-745, 2000.

H. Hemmi, T. Kaisho, O. Takeuchi, S. Sato, H. Sanjo et al., Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway, Nat. Immunol, vol.3, pp.196-200, 2002.

M. J. Hendrix, E. A. Seftor, Y. W. Chu, K. T. Trevor, and R. E. Seftor, Role of intermediate filaments in migration, invasion and metastasis, Cancer Metastasis Rev, vol.15, pp.507-525, 1996.

C. J. Hertz, Q. Wu, E. M. Porter, Y. J. Zhang, K. Weismüller et al., , 2003.

D. A. Hildeman, T. Mitchell, B. Aronow, S. Wojciechowski, J. Kappler et al., Control of Bcl-2 expression by reactive oxygen species, Proc. Natl. Acad. Sci. U. S. A, vol.100, pp.15035-15040, 2003.

V. Ho, T. S. Lim, J. Lee, J. Steinberg, R. Szmyd et al., TLR3 agonist and Sorafenib combinatorial therapy promotes immune activation and controls hepatocellular carcinoma progression, Oncotarget, 2015.

B. Hoechst, L. A. Ormandy, M. Ballmaier, F. Lehner, C. Krüger et al., , 2008.

R. F. Hoffmann, S. Zarrintan, S. M. Brandenburg, A. Kol, H. G. De-bruin et al., Prolonged cigarette smoke exposure alters mitochondrial structure and function in airway epithelial cells, Respir. Res, vol.14, p.97, 2013.

M. Holcmann, B. Drobits, and M. Sibilia, How imiquimod licenses plasmacytoid dendritic cells to kill tumors, Oncoimmunology, vol.1, pp.1661-1663, 2012.

D. Hongo, X. Tang, J. Baker, E. G. Engleman, and S. Strober, Requirement for interactions of natural killer T cells and myeloid-derived suppressor cells for transplantation tolerance, Am. J. Transplant. Off. J. Am. Soc. Transplant. Am. Soc. Transpl. Surg, vol.14, pp.2467-2477, 2014.

P. A. Hopkins and S. Sriskandan, Mammalian Toll-like receptors: to immunity and beyond, Clin. Exp. Immunol, vol.140, pp.395-407, 2005.

M. W. Hornef, B. H. Normark, A. Vandewalle, and S. Normark, Intracellular recognition of lipopolysaccharide by toll-like receptor 4 in intestinal epithelial cells, J. Exp. Med, vol.198, pp.1225-1235, 2003.

V. Hornung, S. Rothenfusser, S. Britsch, A. Krug, B. Jahrsdörfer et al., , 2002.

, J. Immunol. Baltim. Md, vol.168, pp.4531-4537, 1950.

V. Hornung, M. Guenthner-biller, C. Bourquin, A. Ablasser, M. Schlee et al., Sequence-specific potent induction of IFN-alpha by short interfering RNA in plasmacytoid dendritic cells through TLR7, Nat. Med, vol.11, pp.263-270, 2005.

V. Hornung, J. Ellegast, S. Kim, K. Brzózka, A. Jung et al., 5'-Triphosphate RNA is the ligand for RIG-I, Science, vol.314, pp.994-997, 2006.

K. Hoshino, O. Takeuchi, T. Kawai, H. Sanjo, T. Ogawa et al., Pillars Article: Cutting Edge: Toll-Like Receptor 4 (TLR4)-Deficient Mice Are Hyporesponsive to Lipopolysaccharide: Evidence for TLR4 as the Lps Gene Product, J. Immunol. Baltim. Md, vol.162, pp.2563-2566, 1999.

C. Hsiao, P. Chen, C. Cheng, M. Tsai, C. Chang et al., , 2015.

B. Huang, J. Zhao, H. Li, K. He, Y. Chen et al., , 2005.

B. Huang, P. Pan, Q. Li, A. I. Sato, D. E. Levy et al., Gr-1+CD115+ immature myeloid suppressor cells mediate the development of tumor-induced T regulatory cells and T-cell anergy in tumor-bearing host, Cancer Res, vol.66, pp.1123-1131, 2006.

B. Huang, J. Zhao, S. Shen, H. Li, K. He et al., , 2007.

B. Huang, J. Zhao, J. C. Unkeless, Z. H. Feng, and H. Xiong, TLR signaling by tumor and immune cells: a double-edged sword, Oncogene, vol.27, pp.218-224, 2008.

M. Huang, W. Lin, and Y. Ma, , 2005.

S. Huang, W. Wei, Y. , and Y. , Upregulation of TLR7 and TLR3 gene expression in the lung of respiratory syncytial virus infected mice, Wei Sheng Wu Xue Bao, vol.49, pp.239-245, 2009.

A. O. Huen and A. H. Rook, Toll receptor agonist therapy of skin cancer and cutaneous T-cell lymphoma, Curr. Opin. Oncol, vol.26, pp.237-244, 2014.

N. Husseinzadeh and S. M. Davenport, Role of toll-like receptors in cervical, endometrial and ovarian cancers: a review, Gynecol. Oncol, vol.135, pp.359-363, 2014.

E. Ichihara, K. Hotta, N. Nogami, S. Kuyama, D. Kishino et al., mutations: the Okayama Lung Cancer Study Group Trial 1001, J. Thorac. Oncol. Off. Publ. Int. Assoc. Study Lung Cancer, vol.10, pp.486-491, 2015.

M. Ichikawa, R. Williams, L. Wang, T. Vogl, and G. Srikrishna, S100A8/A9 activate key genes and pathways in colon tumor progression, Mol. Cancer Res. MCR, vol.9, p.133, 2011.

K. Imai, S. Matsuyama, S. Miyake, K. Suga, and K. Nakachi, Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence: an 11-year follow-up study of a general population, Lancet Lond. Engl, vol.356, pp.1795-1799, 2000.

N. Ito, Y. Suzuki, Y. Taniguchi, K. Ishiguro, H. Nakamura et al., , 2005.

, Anticancer Res, vol.25, pp.2027-2031

B. Jahrsdörfer, J. E. Wooldridge, S. E. Blackwell, C. M. Taylor, T. S. Griffith et al., Immunostimulatory oligodeoxynucleotides induce apoptosis of B cell chronic lymphocytic leukemia cells, J. Leukoc. Biol, vol.77, pp.378-387, 2005.

S. Jain, S. Suklabaidya, B. Das, S. K. Raghav, S. K. Batra et al., TLR4 Prostate, vol.75, pp.1020-1033, 2015.

C. A. Janeway, Approaching the asymptote? Evolution and revolution in immunology, Cold Spring Harb. Symp. Quant. Biol. 54 Pt, vol.1, pp.1-13, 1989.

G. Jego, R. Bataille, A. Geffroy-luseau, G. Descamps, and C. Pellat-deceunynck, , 2006.

, Pathogen-associated molecular patterns are growth and survival factors for human myeloma cells through Toll-like receptors, Leukemia, vol.20, pp.1130-1137

Q. Jiang, H. Wei, and Z. Tian, Poly I:C enhances cycloheximide-induced apoptosis, 2008.

D. Y. Jin, F. Spencer, and K. T. Jeang, , 1998.

L. Johnson, K. Mercer, D. Greenbaum, R. T. Bronson, D. Crowley et al., Somatic activation of the K-ras oncogene causes early onset lung cancer in mice, Nature, vol.410, pp.1111-1116, 2001.

W. J. De-jonge, K. L. Kwikkers, A. A. Te-velde, S. J. Van-deventer, M. A. Nolte et al., Arginine deficiency affects early B cell maturation and lymphoid organ development in transgenic mice, J. Clin. Invest, vol.110, pp.1539-1548, 2002.

J. A. Joyce and J. W. Pollard, Microenvironmental regulation of metastasis, Nat. Rev. Cancer, vol.9, pp.239-252, 2009.

M. L. Kalb, A. Glaser, G. Stary, F. Koszik, and G. Stingl, TRAIL(+) human plasmacytoid dendritic cells kill tumor cells in vitro: mechanisms of imiquimod-and IFN-?-mediated antitumor reactivity, J. Immunol. Baltim. Md, vol.188, pp.1583-1591, 1950.

A. Kao, K. Wang, C. Long, C. Chai, C. Tsai et al., , 2011.

M. Karin, Nuclear factor-kappaB in cancer development and progression, Nature, vol.441, pp.431-436, 2006.

T. Kawagoe, S. Sato, K. Matsushita, H. Kato, K. Matsui et al., Sequential control of Toll-like receptor-dependent responses by IRAK1 and IRAK2, Nat. Immunol, vol.9, pp.684-691, 2008.

T. Kawai, S. Akira, N. D. Leigh, G. Bian, X. Ding et al., The role of pattern-recognition receptors in innate immunity, 2010.

B. Lemaitre, E. Nicolas, L. Michaut, J. M. Reichhart, and J. A. Hoffmann, , 1996.

E. J. Leonard, A. Skeel, Y. , and T. , Biological aspects of monocyte chemoattractant protein-1 (MCP-1), Adv. Exp. Med. Biol, vol.305, pp.57-64, 1991.

H. Li, Y. Han, Q. Guo, M. Zhang, and X. Cao, Cancer-expanded myeloid-derived suppressor cells induce anergy of NK cells through membrane-bound TGF-beta 1, J. Immunol. Baltim. Md, vol.182, pp.240-249, 1950.

S. Li, R. Sun, Y. Chen, H. Wei, and Z. Tian, TLR2 limits development of hepatocellular carcinoma by reducing IL18-mediated immunosuppression, Cancer Res, vol.75, pp.986-995, 2015.

X. Li, S. Wang, R. Zhu, H. Li, Q. Han et al., , 2016.

E. Y. Lin, J. Li, L. Gnatovskiy, Y. Deng, L. Zhu et al., Res, vol.66, pp.11238-11246, 2006.

H. Lin, J. Yan, Z. Wang, F. Hua, J. Yu et al.,

C. Liu, Y. Lou, G. Lizée, H. Qin, S. Liu et al., Plasmacytoid dendritic cells induce NK cell-dependent, tumor antigen-specific T cell cross-priming and tumor regression in mice, J. Clin. Invest, vol.118, pp.1165-1175, 2008.

J. Liu, H. Wang, Q. Yu, S. Zheng, Y. Jiang et al., Aberrant frequency of IL-10-producing B cells and its association with Treg and MDSC cells in Non Small Cell Lung Carcinoma patients, Hum. Immunol, vol.77, pp.84-89, 2016.

Y. Liu, W. Yan, S. Tohme, M. Chen, Y. Fu et al.,

, Hypoxia induced HMGB1 and mitochondrial DNA interactions mediate tumor growth in hepatocellular carcinoma through Toll-like receptor 9, J. Hepatol, vol.63, pp.114-121

K. B. Long and G. L. Beatty, Harnessing the antitumor potential of macrophages for cancer immunotherapy, Oncoimmunology, vol.2, p.26860, 2013.

E. L. Lowe, T. R. Crother, S. Rabizadeh, B. Hu, H. Wang et al., , p.13027, 2010.

J. M. Lund, L. Alexopoulou, A. Sato, M. Karow, N. C. Adams et al., Recognition of single-stranded RNA viruses by Toll-like receptor 7, 2004.

, Proc. Natl. Acad. Sci. U. S. A, vol.101, pp.5598-5603

Y. Luo, Q. Jiang, J. Wu, J. Qiu, W. Zhang et al.,

T. J. Lynch, I. Bondarenko, A. Luft, P. Serwatowski, F. Barlesi et al., Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage IIIB/IV non-small-cell lung cancer: results from a randomized, double-blind, multicenter phase II study, J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol, vol.30, pp.2046-2054, 2012.

F. Ma, Z. Liu, X. Hu, H. Ling, S. Li et al., , 2014.

C. W. Mai, Y. B. Kang, and M. R. Pichika, Should a Toll-like receptor 4 (TLR-4) agonist or antagonist be designed to treat cancer? TLR-4: its expression and effects in the ten most common cancers, OncoTargets Ther, vol.6, pp.1573-1587, 2013.

B. Manicassamy, S. Manicassamy, A. Belicha-villanueva, G. Pisanelli, B. Pulendran et al., Analysis of in vivo dynamics of influenza virus infection in mice using a GFP reporter virus, Proc. Natl. Acad. Sci. U. S. A, vol.107, pp.11531-11536, 2010.

A. Mantovani, B. Bottazzi, F. Colotta, S. Sozzani, and L. Ruco, The origin and function of tumor-associated macrophages, Immunol. Today, vol.13, pp.265-270, 1992.

A. Mantovani, P. Allavena, A. Sica, and F. Balkwill, Cancer-related inflammation, Nature, vol.454, pp.436-444, 2008.

I. Marigo, E. Bosio, S. Solito, C. Mesa, A. Fernandez et al., Tumor-induced tolerance and immune suppression depend on the C/EBPbeta transcription factor, Immunity, vol.32, pp.790-802, 2010.

M. U. Martin and H. Wesche, Summary and comparison of the signaling mechanisms of the Toll/interleukin-1 receptor family, Biochim. Biophys. Acta, vol.1592, pp.265-280, 2002.

A. Maruyama, H. Shime, Y. Takeda, M. Azuma, M. Matsumoto et al., , 2015.

, Pam2 lipopeptides systemically increase myeloid-derived suppressor cells through TLR2 signaling, Biochem. Biophys. Res. Commun, vol.457, pp.445-450

S. Maschalidi, S. Hässler, F. Blanc, F. E. Sepulveda, M. Tohme et al., Asparagine endopeptidase controls anti-influenza virus immune responses through TLR7 activation, PLoS Pathog, vol.8, p.1002841, 2012.

T. Matijevic, M. Marjanovic, and J. Pavelic, Functionally active toll-like receptor 3 on human primary and metastatic cancer cells, Scand. J. Immunol, vol.70, pp.18-24, 2009.

A. Mazzoni, V. Bronte, A. Visintin, J. H. Spitzer, E. Apolloni et al., Myeloid suppressor lines inhibit T cell responses by an NOdependent mechanism, J. Immunol. Baltim. Md, vol.168, pp.689-695, 1950.

R. Medzhitov, P. Preston-hurlburt, and C. A. Janeway, A human homologue of the Drosophila Toll protein signals activation of adaptive immunity, Nature, vol.388, pp.394-397, 1997.

L. B. Meira, J. M. Bugni, S. L. Green, C. Lee, B. Pang et al., DNA damage induced by chronic inflammation contributes to colon carcinogenesis in mice, J. Clin. Invest, vol.118, pp.2516-2525, 2008.

M. Miettinen, T. Sareneva, I. Julkunen, and S. Matikainen, IFNs activate toll-like receptor gene expression in viral infections, Genes Immun, vol.2, pp.349-355, 2001.

K. Milne, M. Köbel, S. E. Kalloger, R. O. Barnes, D. Gao et al., Systematic analysis of immune infiltrates in high-grade serous ovarian cancer reveals CD20, FoxP3 and TIA-1 as positive prognostic factors, PloS One, vol.4, p.6412, 2009.

K. Miyake, Endotoxin recognition molecules, Toll-like receptor 4-MD-2, Semin. Immunol, vol.16, pp.11-16, 2004.

T. S. Mok, Y. Wu, S. Thongprasert, C. Yang, D. Chu et al., Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma, N. Engl. J. Med, vol.361, pp.947-957, 2009.

M. Molteni, D. Marabella, C. Orlandi, and C. Rossetti, Melanoma cell lines are responsive in vitro to lipopolysaccharide and express TLR-4, Cancer Lett, vol.235, pp.75-83, 2006.

J. K. Morales, M. Kmieciak, K. L. Knutson, H. D. Bear, and M. H. Manjili, GM-CSF, 2010.

D. Moreira, Q. Zhang, D. M. Hossain, S. Nechaev, H. Li et al., TLR9 signaling through NF-?B/RELA and STAT3 promotes tumor-propagating potential of prostate cancer cells, Oncotarget, vol.6, pp.17302-17313, 2015.

M. Muccioli and F. Benencia, Toll-like Receptors in Ovarian Cancer as Targets for Immunotherapies, Front. Immunol, vol.5, p.341, 2014.

A. Muir, G. Soong, S. Sokol, B. Reddy, M. I. Gomez et al.,

, Toll-like receptors in normal and cystic fibrosis airway epithelial cells, Am. J. Respir. Cell Mol. Biol, vol.30, pp.777-783

C. Murdoch, M. Muthana, S. B. Coffelt, and C. E. Lewis, The role of myeloid cells in the promotion of tumour angiogenesis, Nat. Rev. Cancer, vol.8, pp.618-631, 2008.

H. Nagase, S. Okugawa, Y. Ota, M. Yamaguchi, H. Tomizawa et al., Expression and function of Toll-like receptors in eosinophils: activation by Toll-like receptor 7 ligand, J. Immunol. Baltim. Md, vol.171, pp.3977-3982, 1950.

T. Nakajima, N. Mizushima, J. Nakamura, and K. Kanai, Surface markers of NK cells in peripheral blood of patients with cirrhosis and hepatocellular carcinoma, Immunol. Lett, vol.13, pp.7-10, 1986.

H. Nakshatri, P. Bhat-nakshatri, D. A. Martin, R. J. Goulet, and G. W. Sledge, , 1997.

M. Naseemuddin, A. Iqbal, T. H. Nasti, J. L. Ghandhi, A. D. Kapadia et al., , 2012.

, Cell mediated immune responses through TLR4 prevents DMBA-induced mammary carcinogenesis in mice, Int. J. Cancer J. Int. Cancer, vol.130, pp.765-774

A. A. Navarini-meury, C. , and C. , Melanoma and innate immunity--aActive inflammation or just erroneous attraction? Melanoma as the source of leukocyte-attracting chemokines, Semin. Cancer Biol, vol.19, pp.84-91, 2009.

R. P. Negus, G. W. Stamp, J. Hadley, and F. R. Balkwill, Quantitative assessment of the leukocyte infiltrate in ovarian cancer and its relationship to the expression of C-C chemokines, Am. J. Pathol, vol.150, pp.1723-1734, 1997.

M. F. Neurath and S. Finotto, IL-6 signaling in autoimmunity, chronic inflammation and inflammation-associated cancer, Cytokine Growth Factor Rev, vol.22, pp.83-89, 2011.

K. Newton and V. M. Dixit, Signaling in innate immunity and inflammation, Cold Spring Harb. Perspect. Biol, vol.4, 2012.

J. S. Nielsen, R. A. Sahota, K. Milne, S. E. Kost, N. J. Nesslinger et al., CD20+ tumor-infiltrating lymphocytes have an atypical CD27-memory phenotype and together with CD8+ T cells promote favorable prognosis in ovarian cancer, 2012.

, Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res, vol.18, pp.3281-3292

N. Nomi, S. Kodama, and M. Suzuki, , 2010.

C. Norbet, A. Joseph, S. S. Rossi, S. Bhalla, and F. R. Gutierrez, Asbestos-related lung disease: a pictorial review, Curr. Probl. Diagn. Radiol, vol.44, pp.371-382, 2015.

N. Obermajer, R. Muthuswamy, K. Odunsi, R. P. Edwards, and P. Kalinski, , 2011.

A. Ochi, C. S. Graffeo, C. P. Zambirinis, A. Rehman, M. Hackman et al., Toll-like receptor 7 regulates pancreatic carcinogenesis in mice and humans, J. Clin. Invest, vol.122, pp.4118-4129, 2012.

J. B. Ochoa, J. Strange, P. Kearney, G. Gellin, E. Endean et al., Effects of L-arginine on the proliferation of T lymphocyte subpopulations, JPEN J. Parenter. Enteral Nutr, vol.25, pp.23-29, 2001.

M. Okamoto, T. Oshikawa, T. Tano, G. Ohe, S. Furuichi et al., Involvement of Toll-like receptor 4 signaling in interferon-gamma production and antitumor effect by streptococcal agent OK, 2003.

, J. Natl. Cancer Inst, vol.95, pp.316-326

I. S. Okon, K. A. Coughlan, M. Zhang, Q. Wang, and M. Zou, , 2015.

P. B. Olkhanud, B. Damdinsuren, M. Bodogai, R. E. Gress, R. Sen et al., Tumor-evoked regulatory B cells promote breast cancer metastasis by converting resting CD4, 2011.

, + T cells to T-regulatory cells, Cancer Res, vol.71, pp.3505-3515

S. Onizuka, I. Tawara, J. Shimizu, S. Sakaguchi, T. Fujita et al., , 1999.

M. Oosting, S. Cheng, J. M. Bolscher, R. Vestering-stenger, T. S. Plantinga et al., Human TLR10 is an anti-inflammatory pattern-recognition receptor, Proc. Natl. Acad. Sci. U. S. A, vol.111, pp.4478-4484, 2014.

A. Orimo, P. B. Gupta, D. C. Sgroi, F. Arenzana-seisdedos, T. Delaunay et al., , 2005.

A. Ozinsky, D. M. Underhill, J. D. Fontenot, A. M. Hajjar, K. D. Smith et al., , 2000.

A. S. Pak, M. A. Wright, J. P. Matthews, S. L. Collins, G. J. Petruzzelli et al.,

, Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res, vol.1, pp.95-103

A. Paone, D. Starace, R. Galli, F. Padula, P. De-cesaris et al., Toll-like receptor 3 triggers apoptosis of human prostate cancer cells through a PKC-alpha-dependent mechanism, Carcinogenesis, vol.29, pp.1334-1342, 2008.

E. J. Park, J. H. Lee, G. Yu, G. He, S. R. Ali et al., Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL-6 and TNF expression, Cell, vol.140, pp.197-208, 2010.

J. Park, H. Yoon, D. Kim, S. Kim, S. Ahn et al., Tolllike receptor 5 activation promotes migration and invasion of salivary gland adenocarcinoma, 2011.

, J. Oral Pathol. Med. Off. Publ. Int. Assoc. Oral Pathol. Am. Acad. Oral Pathol, vol.40, pp.187-193

D. M. Parkin, The global health burden of infection-associated cancers in the year 2002, Int. J. Cancer, vol.118, pp.3030-3044, 2006.

R. D. Pawar, A. Ramanjaneyulu, O. P. Kulkarni, M. Lech, S. Segerer et al.,

, J. Am. Soc. Nephrol. JASN, vol.18, pp.1721-1731

I. Perrot, D. Blanchard, N. Freymond, S. Isaac, B. Guibert et al.,

, J. Immunol. Baltim. Md, vol.178, pp.2763-2769, 1950.

R. P. Petersen, M. J. Campa, J. Sperlazza, D. Conlon, M. Joshi et al., Tumor infiltrating Foxp3+ regulatory T-cells are associated with recurrence in pathologic stage I NSCLC patients, Cancer, vol.107, pp.2866-2872, 2006.

A. Pichlmair, O. Schulz, C. P. Tan, T. I. Näslund, P. Liljeström et al., RIG-I-mediated antiviral responses to single-stranded RNA bearing 5'-phosphates, Science, vol.314, pp.997-1001, 2006.

E. Pikarsky, R. M. Porat, I. Stein, R. Abramovitch, S. Amit et al., NF-kappaB functions as a tumour promoter in inflammation-associated cancer, Nature, vol.431, pp.461-466, 2004.

M. R. Pillai, A. Phanidhara, A. L. Kesari, P. Nair, and M. K. Nair, Cellular manifestations of human papillomavirus infection in the oral mucosa, J. Surg. Oncol, vol.71, p.10, 1999.

P. Pimentel-nunes, L. Afonso, P. Lopes, R. Roncon-albuquerque, N. Gonçalves et al., Increased expression of toll-like receptors (TLR) 2, 4 and 5 in gastric dysplasia, Pathol. Oncol. Res. POR, vol.17, pp.677-683, 2011.

C. A. Pise-masison, K. S. Choi, M. Radonovich, J. Dittmer, S. J. Kim et al.,

, Virol, vol.72, pp.1165-1170

S. Platonova, J. Cherfils-vicini, D. Damotte, L. Crozet, V. Vieillard et al., Profound coordinated alterations of intratumoral NK cell phenotype and function in lung carcinoma, Cancer Res, vol.71, pp.5412-5422, 2011.

B. J. Poiesz, F. W. Ruscetti, A. F. Gazdar, P. A. Bunn, J. D. Minna et al., cutaneous T-cell lymphoma, Proc. Natl. Acad. Sci. U. S. A, vol.77, pp.7415-7419, 1980.

J. W. Pollard, Tumour-educated macrophages promote tumour progression and metastasis, Nat. Rev. Cancer, vol.4, pp.71-78, 2004.

A. Poltorak, X. He, I. Smirnova, M. Y. Liu, C. Van-huffel et al., Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene, Science, vol.282, pp.2085-2088, 1998.

M. R. Porembka, J. B. Mitchem, B. A. Belt, C. Hsieh, H. Lee et al., Pancreatic adenocarcinoma induces bone marrow mobilization of myeloid-derived suppressor cells which promote primary tumor growth, Cancer Immunol. Immunother. CII, vol.61, pp.1373-1385, 2012.

L. Qian, G. Bian, Y. Zhou, Y. Wang, J. Hu et al., , 2015.

Z. Qin, G. Richter, T. Schüler, S. Ibe, X. Cao et al., B cells inhibit induction of T cell-dependent tumor immunity, Nat. Med, vol.4, pp.627-630, 1998.

R. Radi, Nitric oxide, oxidants, and protein tyrosine nitration, Proc. Natl. Acad. Sci. U. S. A, vol.101, pp.4003-4008, 2004.

S. Rakoff-nahoum, Why cancer and inflammation? Yale, J. Biol. Med, vol.79, pp.123-130, 2006.

S. Rakoff-nahoum and R. Medzhitov, Toll-like receptors and cancer, Nat. Rev. Cancer, vol.9, pp.57-63, 2009.

S. P. Rao, J. Sancho, J. Campos-rivera, P. M. Boutin, P. B. Severy et al., Human Peripheral Blood Mononuclear Cells Exhibit Heterogeneous CD52 Expression Levels and Show Differential Sensitivity to Alemtuzumab Mediated Cytolysis, PLoS ONE, vol.7, 2012.

A. Ray, K. Chakraborty, and P. Ray, Immunosuppressive MDSCs induced by TLR signaling during infection and role in resolution of inflammation, Front. Cell. Infect. Microbiol, vol.3, p.52, 2013.

T. Regan, K. Nally, R. Carmody, A. Houston, F. Shanahan et al.,

, intestinal epithelial cells and macrophages, J. Immunol. Baltim. Md, pp.6084-6092, 1950191.

S. H. Rhee, E. Im, and C. Pothoulakis, , 2008.

J. C. Roach, G. Glusman, L. Rowen, A. Kaur, M. K. Purcell et al., The evolution of vertebrate Toll-like receptors, Proc. Natl. Acad. Sci. U. S. A, vol.102, pp.9577-9582, 2005.

S. J. Roberts, B. Y. Ng, R. B. Filler, J. Lewis, E. J. Glusac et al., Characterizing tumor-promoting T cells in chemically induced cutaneous carcinogenesis, Proc. Natl. Acad. Sci. U. S. A, vol.104, pp.6770-6775, 2007.

F. L. Rock, G. Hardiman, J. C. Timans, R. A. Kastelein, and J. F. Bazan, A family of human receptors structurally related to Drosophila Toll, Proc. Natl. Acad. Sci. U. S. A, vol.95, pp.588-593, 1998.

J. C. Roder, T. Haliotis, M. Klein, S. Korec, J. R. Jett et al., A new immunodeficiency disorder in humans involving NK cells, Nature, vol.284, pp.553-555, 1980.

P. C. Rodriguez, D. G. Quiceno, J. Zabaleta, B. Ortiz, A. H. Zea et al., , 2004.

B. J. Rollins, T. Yoshimura, E. J. Leonard, and J. S. Pober, Cytokine-activated human endothelial cells synthesize and secrete a monocyte chemoattractant, MCP-1/JE, Am. J. Pathol, vol.136, pp.1229-1233, 1990.

H. Ronkainen, P. Hirvikoski, S. Kauppila, K. S. Vuopala, T. K. Paavonen et al., Absent Toll-like receptor-9 expression predicts poor prognosis in renal cell carcinoma, J. Exp. Clin. Cancer Res. CR, vol.30, p.84, 2011.

R. Rosell, T. Moran, C. Queralt, R. Porta, F. Cardenal et al., Screening for epidermal growth factor receptor mutations in lung cancer, N. Engl. J. Med, vol.361, pp.958-967, 2009.

R. Rosell, E. Carcereny, R. Gervais, A. Vergnenegre, B. Massuti et al., Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutationpositive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial, Lancet Oncol, vol.13, pp.239-246, 2012.

M. R. Rutkowski, T. L. Stephen, N. Svoronos, M. J. Allegrezza, A. J. Tesone et al., , 2015.

M. Sade-feldman, J. Kanterman, E. Ish-shalom, M. Elnekave, E. Horwitz et al., Tumor necrosis factor-? blocks differentiation and enhances suppressive activity of immature myeloid cells during chronic inflammation, Immunity, vol.38, pp.541-554, 2013.

B. Salaun, S. Lebecque, S. Matikainen, D. Rimoldi, and P. Romero, Toll-like receptor 3 expressed by melanoma cells as a target for therapy? Clin, Cancer Res. Off. J. Am, 2007.

. Assoc, Cancer Res, vol.13, pp.4565-4574

T. Sato, T. Shimosato, A. Ueda, Y. Ishigatsubo, and D. M. Klinman, , 2015.

, Intrapulmonary Delivery of CpG Microparticles Eliminates Lung Tumors, Mol. Cancer Ther, vol.14, pp.2198-2205

Y. Sato, Y. Goto, N. Narita, and D. S. Hoon, Cancer Cells Expressing Toll-like Receptors and the Tumor Microenvironment, Cancer Microenviron. Off. J. Int. Cancer Microenviron. Soc, vol.2, pp.205-214, 2009.

S. P. Schantz, E. J. Shillitoe, B. Brown, and B. Campbell, Natural killer cell activity and head and neck cancer: a clinical assessment, J. Natl. Cancer Inst, vol.77, pp.869-875, 1986.

F. A. Scheeren, A. H. Kuo, L. J. Van-weele, S. Cai, I. Glykofridis et al., A cell-intrinsic role for TLR2-MYD88 in intestinal and breast epithelia and oncogenesis, Nat. Cell Biol, vol.16, pp.1238-1248, 2014.

B. Schmausser, M. Andrulis, S. Endrich, H. Müller-hermelink, and M. Eck, , 2005.

, Toll-like receptors TLR4, TLR5 and TLR9 on gastric carcinoma cells: an implication for interaction with Helicobacter pylori, Int. J. Med. Microbiol. IJMM, vol.295, pp.179-185

M. C. Schmid and J. A. Varner, Myeloid cells in the tumor microenvironment: modulation of tumor angiogenesis and tumor inflammation, J. Oncol, 2010.

L. H. Schmidt, A. Kümmel, D. Görlich, M. Mohr, S. Bröckling et al., PD-1 and PD-L1 Expression in NSCLC Indicate a Favorable Prognosis in Defined Subgroups, PloS One, vol.10, 2015.

M. Schmidt, B. Hellwig, S. Hammad, A. Othman, M. Lohr et al., Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res, vol.18, pp.2695-2703, 2012.

F. J. Schopfer, P. R. Baker, and B. A. Freeman, NO-dependent protein nitration: a cell signaling event or an oxidative inflammatory response?, Trends Biochem. Sci, vol.28, pp.646-654, 2003.

S. F. Schoppmann, P. Birner, J. Stöckl, R. Kalt, R. Ullrich et al., Tumor-associated macrophages express lymphatic endothelial growth factors and are related to peritumoral lymphangiogenesis, Am. J. Pathol, vol.161, pp.947-956, 2002.

H. J. Schulze, B. Cribier, L. Requena, J. Reifenberger, C. Ferrándiz et al., Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: results from a randomized vehicle-controlled phase III study in Europe, Br. J. Dermatol, vol.152, pp.939-947, 2005.

M. Seitz, P. Loetscher, B. Dewald, H. Towbin, H. Gallati et al., Interleukin-10 differentially regulates cytokine inhibitor and chemokine release from blood mononuclear cells and fibroblasts, Eur. J. Immunol, vol.25, pp.1129-1132, 1995.

P. Serafini, R. Carbley, K. A. Noonan, G. Tan, V. Bronte et al., Highdose granulocyte-macrophage colony-stimulating factor-producing vaccines impair the immune response through the recruitment of myeloid suppressor cells, Cancer Res, vol.64, pp.6337-6343, 2004.

T. Seto, T. Kato, M. Nishio, K. Goto, S. Atagi et al., Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): an open-label, randomised, multicentre, phase 2 study, Lancet Oncol, vol.15, pp.1236-1244, 2014.

M. Shackleton, I. D. Davis, W. Hopkins, H. Jackson, N. Dimopoulos et al., The impact of imiquimod, 2004.

S. Shah, A. A. Divekar, S. P. Hilchey, H. Cho, C. L. Newman et al., Increased rejection of primary tumors in mice lacking B cells: inhibition of anti-tumor CTL and TH1 cytokine responses by B cells, Int. J. Cancer, vol.117, pp.574-586, 2005.

V. Shankaran, H. Ikeda, A. T. Bruce, J. M. White, P. E. Swanson et al., IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity, Nature, vol.410, pp.1107-1111, 2001.

Y. Shao, C. M. Lo, C. C. Ling, X. B. Liu, K. T. Ng et al., Regulatory B cells accelerate hepatocellular carcinoma progression via CD40/CD154 signaling pathway, Cancer Lett, vol.355, pp.264-272, 2014.

H. Shen and V. Tergaonkar, NFkappaB signaling in carcinogenesis and as a potential molecular target for cancer therapy, Apoptosis Int. J. Program. Cell Death, vol.14, pp.348-363, 2009.

W. Shi, L. Su, Q. Li, L. Sun, J. Lv et al., Suppression of toll-like receptor 2 expression inhibits the bioactivity of human hepatocellular carcinoma, Tumour Biol. J. Int. Soc. Oncodevelopmental Biol. Med, vol.35, pp.9627-9637, 2014.

A. Shimabukuro-vornhagen, H. A. Schlößer, L. Gryschok, J. Malcher, K. Wennhold et al., , 2014.

H. Shime, M. Matsumoto, H. Oshiumi, S. Tanaka, A. Nakane et al., Toll-like receptor 3 signaling converts tumor-supporting myeloid cells to tumoricidal effectors, Proc. Natl. Acad. Sci. U. S. A, vol.109, pp.2066-2071, 2012.

J. Shimizu, S. Yamazaki, and S. Sakaguchi, Induction of tumor immunity by removing CD25+CD4+ T cells: a common basis between tumor immunity and autoimmunity, 1999.

, J. Immunol. Baltim. Md, vol.163, pp.5211-5218, 1950.

K. Shimizu, M. Nakata, Y. Hirami, T. Yukawa, A. Maeda et al., , 2010.

H. Shojaei, H. Oberg, M. Juricke, L. Marischen, M. Kunz et al., , 2009.

A. Sica, A. Saccani, B. Bottazzi, N. Polentarutti, A. Vecchi et al., Autocrine production of IL-10 mediates defective IL-12 production and NF-kappa B activation in tumor-associated macrophages, J. Immunol. Baltim. Md, vol.164, pp.762-767, 1950.

A. Sica, P. Allavena, and A. Mantovani, Cancer related inflammation: the macrophage connection, Cancer Lett, vol.267, pp.204-215, 2008.

O. M. Siggs, M. Berger, P. Krebs, C. N. Arnold, C. Eidenschenk et al., A mutation of Ikbkg causes immune deficiency without impairing degradation of IkappaB alpha, Proc. Natl. Acad. Sci. U. S. A, vol.107, pp.3046-3051, 2010.

P. Sinha, V. K. Clements, and S. Ostrand-rosenberg, Reduction of myeloid-derived suppressor cells and induction of M1 macrophages facilitate the rejection of established metastatic disease, J. Immunol. Baltim. Md, vol.174, pp.636-645, 1950.

P. Sinha, V. K. Clements, A. M. Fulton, and S. Ostrand-rosenberg, Prostaglandin E2 promotes tumor progression by inducing myeloid-derived suppressor cells, Cancer Res, vol.67, pp.4507-4513, 2007.

M. Sironi, C. Muñoz, T. Pollicino, A. Siboni, F. L. Sciacca et al., Divergent effects of interleukin-10 on cytokine production by mononuclear phagocytes and endothelial cells, Eur. J. Immunol, vol.23, pp.2692-2695, 1993.

V. Sisirak, J. Faget, M. Gobert, N. Goutagny, N. Vey et al., , 2012.

B. Skaug, X. Jiang, C. , and Z. J. , The role of ubiquitin in NF-kappaB regulatory pathways, Annu. Rev. Biochem, vol.78, pp.769-796, 2009.

D. J. Slamon, G. M. Clark, S. G. Wong, W. J. Levin, A. Ullrich et al., , 1987.

M. J. Smyth, E. Cretney, J. M. Kelly, J. A. Westwood, S. E. Street et al., Activation of NK cell cytotoxicity, Mol. Immunol, vol.42, pp.501-510, 2005.

N. Sonda, M. Chioda, S. Zilio, F. Simonato, and V. Bronte, Transcription factors in myeloid-derived suppressor cell recruitment and function, Curr. Opin. Immunol, vol.23, pp.279-285, 2011.

E. Song, M. Kang, Y. Kim, S. Kim, S. Lee et al., , 2011.

X. Song, Y. Krelin, T. Dvorkin, O. Bjorkdahl, S. Segal et al., CD11b+/Gr-1+ immature myeloid cells mediate suppression of T cells in mice bearing tumors of IL-1beta-secreting cells, J. Immunol. Baltim. Md, vol.175, p.8200, 1950.

M. A. Sovak, R. E. Bellas, D. W. Kim, G. J. Zanieski, A. E. Rogers et al., Aberrant nuclear factor-kappaB/Rel expression and the pathogenesis of breast cancer, J. Clin. Invest, vol.100, pp.2952-2960, 1997.

D. E. Spaner, Y. Shi, D. White, J. Mena, C. Hammond et al., Immunomodulatory effects of Toll-like receptor-7 activation on chronic lymphocytic leukemia cells, Leukemia, vol.20, pp.286-295, 2006.

A. Sparmann and D. Bar-sagi, Ras-induced interleukin-8 expression plays a critical role in tumor growth and angiogenesis, Cancer Cell, vol.6, pp.447-458, 2004.

P. W. Sperduto, N. Kased, D. Roberge, Z. Xu, R. Shanley et al., Summary Report on the Graded Prognostic Assessment: An Accurate and Facile Diagnosis-Specific Tool to Estimate Survival for Patients With Brain Metastases, J. Clin. Oncol, vol.30, pp.419-425, 2012.

M. K. Srivastava, P. Sinha, V. K. Clements, P. Rodriguez, and S. Ostrand-rosenberg,

, Myeloid-derived suppressor cells inhibit T-cell activation by depleting cystine and cysteine, Cancer Res, vol.70, pp.68-77

M. K. Srivastava, L. Zhu, M. Harris-white, U. K. Kar, U. Kar et al., , 2012.

G. Stary, C. Bangert, M. Tauber, R. Strohal, T. Kopp et al., Tumoricidal activity of TLR7/8-activated inflammatory dendritic cells, J. Exp. Med, vol.204, pp.1441-1451, 2007.

W. G. Stetler-stevenson, S. Aznavoorian, and L. A. Liotta, Tumor cell interactions with the extracellular matrix during invasion and metastasis, Annu. Rev. Cell Biol, vol.9, p.541, 1993.

S. E. Stewart, B. E. Eddy, and N. Borgese, Neoplasms in mice inoculated with a tumor agent carried in tissue culture, J. Natl. Cancer Inst, vol.20, pp.1223-1243, 1958.

J. L. Sullivan, K. S. Byron, F. E. Brewster, and D. T. Purtilo, , 1980.

K. Sumida, D. Wakita, Y. Narita, K. Masuko, S. Terada et al., Anti-IL-6 receptor mAb eliminates myeloid-derived suppressor cells and inhibits tumor growth by enhancing T-cell responses, Eur. J. Immunol, vol.42, pp.2060-2072, 2012.

N. Suzuki, S. Suzuki, G. S. Duncan, D. G. Millar, T. Wada et al., Severe impairment of interleukin-1 and Toll-like receptor signalling in mice lacking IRAK-4, Nature, vol.416, pp.750-756, 2002.

J. B. Swann and M. J. Smyth, Immune surveillance of tumors, J. Clin. Invest, vol.117, pp.1137-1146, 2007.

K. J. Syrjänen, Condylomatous changes in neoplastic bronchial epithelium, Int. Rev. Thorac. Dis, vol.38, pp.299-304, 1979.

M. Szczepa?ski, M. Stelmachowska, L. Stryczy?ski, W. Golusi?ski, H. Samara et al., Assessment of expression of toll-like receptors 2, 3 and 4 in laryngeal carcinoma, Eur. Arch. Oto-Rhino-Laryngol. Off. J. Eur. Fed. Oto-RhinoLaryngol. Soc. EUFOS Affil. Ger. Soc. Oto-Rhino-Laryngol. -Head Neck Surg, vol.264, p.525, 2007.

M. J. Szczepanski, M. Czystowska, M. Szajnik, M. Harasymczuk, M. Boyiadzis et al., , 2009.

H. Tye, C. L. Kennedy, M. Najdovska, L. Mcleod, W. Mccormack et al., STAT3-driven upregulation of TLR2 promotes gastric tumorigenesis independent of tumor inflammation, Cancer Cell, vol.22, pp.466-478, 2012.

V. A. Tyurin, W. Cao, Y. Y. Tyurina, D. I. Gabrilovich, and V. E. Kagan, Massspectrometric characterization of peroxidized and hydrolyzed lipids in plasma and dendritic cells of tumor-bearing animals, Biochem. Biophys. Res. Commun, vol.413, pp.149-153, 2011.

D. M. Underhill, A. Ozinsky, A. M. Hajjar, A. Stevens, C. B. Wilson et al., The Toll-like receptor 2 is recruited to macrophage phagosomes and discriminates between pathogens, Nature, vol.401, pp.811-815, 1999.

D. L. Vaux, S. Cory, A. , and J. M. , Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells, Nature, vol.335, pp.440-442, 1988.

V. Velcheti, K. A. Schalper, D. E. Carvajal, V. K. Anagnostou, K. N. Syrigos et al., Programmed death ligand-1 expression in non-small cell lung cancer, Lab. Investig. J. Tech. Methods Pathol, vol.94, pp.107-116, 2014.

E. J. Villablanca, L. Raccosta, D. Zhou, R. Fontana, D. Maggioni et al., , 2010.

E. Vivier, D. H. Raulet, A. Moretta, M. A. Caligiuri, L. Zitvogel et al., Innate or adaptive immunity? The example of natural killer cells, Science, vol.331, pp.44-49, 2011.
URL : https://hal.archives-ouvertes.fr/hal-00611585

I. Voskoboinik, J. C. Whisstock, and J. A. Trapani, Perforin and granzymes: function, dysfunction and human pathology, Nat. Rev. Immunol, vol.15, pp.388-400, 2015.

R. P. Wallin, V. Screpanti, J. Michaëlsson, A. Grandien, and H. Ljunggren, Regulation of perforin-independent NK cell-mediated cytotoxicity, Eur. J. Immunol, vol.33, pp.2727-2735, 2003.

D. Wang, M. Precopio, T. Lan, D. Yu, J. X. Tang et al.,

L. Wang, T. Yi, M. Kortylewski, D. M. Pardoll, D. Zeng et al., IL-17 can promote tumor growth through an IL-6-Stat3 signaling pathway, J. Exp. Med, vol.206, p.1457, 2009.

L. Wang, E. W. Chang, S. C. Wong, S. Ong, D. Q. Chong et al., , 2013.

, /A9 proinflammatory proteins, J. Immunol. Baltim. Md, pp.794-804, 1950190.

W. W. Wang, X. L. Yuan, H. Chen, G. H. Xie, Y. H. Ma et al., CD19+CD24hiCD38hiBregs involved in downregulate helper T cells and upregulate regulatory T cells in gastric cancer, Oncotarget, vol.6, pp.33486-33499, 2015.

X. Wei, Y. Jin, Y. Tian, H. Zhang, J. Wu et al., Regulatory B cells contribute to the impaired antitumor immunity in ovarian cancer patients, Tumour Biol. J. Int. Soc. Oncodevelopmental Biol. Med, vol.37, pp.6581-6588, 2016.

J. R. Woo, M. A. Liss, M. T. Muldong, K. Palazzi, A. Strasner et al., , 2014.

C. Wu, C. Hsieh, C. Lin, W. Chen, J. Hong et al., , 2012.

, J. Mol. Med. Berl. Ger, vol.90, pp.1343-1355

P. Wu, W. D. Dupont, M. R. Griffin, K. N. Carroll, E. F. Mitchel et al., Am. J. Respir. Crit. Care Med, vol.178, pp.1123-1129, 2008.

S. Wu, K. Rhee, E. Albesiano, S. Rabizadeh, X. Wu et al., A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses, Nat. Med, vol.15, pp.1016-1022, 2009.

W. Xie, Y. Wang, Y. Huang, H. Yang, J. Wang et al., Toll-like receptor 2 mediates invasion via activating NF-kappaB in MDA-MB-231 breast cancer cells, Biochem. Biophys. Res. Commun, vol.379, pp.1027-1032, 2009.

Y. Xu, L. Chen, J. Zhou, Y. Wu, and Y. Zhu, Inhibitory effect of dsRNA TLR3 agonist in a rat hepatocellular carcinoma model, Mol. Med. Rep, vol.8, pp.1037-1042, 2013.

F. Yang, Y. Li, T. Wu, N. Na, Y. Zhao et al.,

, TNF?-induced M-MDSCs promote transplant immune tolerance via nitric oxide, J. Mol. Med. Berl. Ger, vol.94, pp.911-920

H. Yang, H. Zhou, P. Feng, X. Zhou, H. Wen et al., ). inflammatory cytokines secretion, J. Exp. Clin. Cancer Res. CR, vol.29, p.92, 2010.

H. Yang, B. Wang, T. Wang, L. Xu, C. He et al., , 2014.

Y. C. Yang, C. L. Chang, Y. W. Huang, and D. Y. Wang, Possible cofactor in cervical carcinogenesis: proliferation index of the transformation zone in cervicitis, 2001.

, J, vol.24, pp.615-620

M. Yao, W. Zhang, Q. Zhang, L. Xing, A. Xu et al., Overexpression of MUC1 enhances proangiogenic activity of non-small-cell lung cancer cells through activation of Akt and extracellular signal-regulated kinase pathways, Lung, vol.189, pp.453-460, 2011.

Y. Yarden and A. Ullrich, Growth factor receptor tyrosine kinases, Annu. Rev. Biochem, vol.57, pp.443-478, 1988.

D. Yesudhas, V. Gosu, M. A. Anwar, and S. Choi, , 2014.

K. Yoneda, K. Sugimoto, K. Shiraki, J. Tanaka, T. Beppu et al., Dual topology of functional Toll-like receptor 3 expression in human hepatocellular carcinoma: differential signaling mechanisms of TLR3-induced NF-kappaB activation and apoptosis, Int. J. Oncol, vol.33, pp.929-936, 2008.

M. Yoshida, I. Miyoshi, and Y. Hinuma, Isolation and characterization of retrovirus from cell lines of human adult T-cell leukemia and its implication in the disease, Proc. Natl, 1982.

J. Youn and D. I. Gabrilovich, The biology of myeloid-derived suppressor cells: the blessing and the curse of morphological and functional heterogeneity, Eur. J. Immunol, vol.40, pp.2969-2975, 2010.

R. P. Young and R. J. Hopkins, Link between COPD and lung cancer, Respir. Med, vol.104, pp.758-759, 2010.

H. Yu, D. Pardoll, J. , and R. , STATs in cancer inflammation and immunity: a leading role for STAT3, Nat. Rev. Cancer, vol.9, pp.798-809, 2009.

A. Yuan, Y. Hsiao, H. Chen, H. Chen, C. Ho et al., Opposite Effects of M1 and M2 Macrophage Subtypes on, Lung Cancer Progression. Sci. Rep, vol.5, p.14273, 2015.

N. Yusuf, T. H. Nasti, J. A. Long, M. Naseemuddin, A. P. Lucas et al.,

C. P. Zambirinis, E. Levie, S. Nguy, A. Avanzi, R. Barilla et al., TLR9 ligation in pancreatic stellate cells promotes tumorigenesis, J. Exp. Med, vol.212, pp.2077-2094, 2015.

A. H. Zea, P. C. Rodriguez, M. B. Atkins, C. Hernandez, S. Signoretti et al., Arginase-producing myeloid suppressor cells in renal cell carcinoma patients: a mechanism of tumor evasion, Cancer Res, vol.65, pp.3044-3048, 2005.

S. M. Zeisberger, B. Odermatt, C. Marty, A. H. Zehnder-fjällman, K. Ballmer-hofer et al., Clodronate-liposome-mediated depletion of tumourassociated macrophages: a new and highly effective antiangiogenic therapy approach, Br. J. Cancer, vol.95, pp.272-281, 2006.

J. Zhang, L. Patel, and K. J. Pienta, CC chemokine ligand 2 (CCL2) promotes prostate cancer tumorigenesis and metastasis, Cytokine Growth Factor Rev, vol.21, pp.41-48, 2010.

Y. Zhang, F. Luo, Y. Cai, N. Liu, L. Wang et al., , 2011.

, J. Immunol. Baltim. Md, vol.186, pp.1963-1969, 1950.

Y. Zhang, Q. Wang, A. Ma, Y. Li, R. Li et al., Functional expression of TLR9 in esophageal cancer, Oncol. Rep, vol.31, pp.2298-2304, 2014.

Z. Zhao, X. Cheng, Y. Wang, R. Han, L. Li et al., Metformin inhibits the IL-6-induced epithelial-mesenchymal transition and lung adenocarcinoma growth and metastasis, PloS One, vol.9, p.95884, 2014.

C. Zhou, Y. Wu, G. Chen, J. Feng, X. Liu et al., Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study, Lancet Oncol, vol.12, pp.735-742, 2011.

J. Zhou, Z. Min, D. Zhang, W. Wang, F. Marincola et al., Enhanced frequency and potential mechanism of B regulatory cells in patients with lung cancer, J. Transl. Med, vol.12, p.304, 2014.

S. Zhou, F. Li, Y. Qiao, X. Zhang, and Z. Wang, J. Cancer Prev. APJCP, vol.13, pp.2807-2812, 2012.

X. Zhou, Y. Su, X. Lao, Y. Liang, and G. Liao, CD19(+)IL-10(+), 2016.

Z. Zhou, X. Yu, J. Zhang, Z. Tian, and C. Zhang, TLR7/8 agonists promote NK-DC cross-talk to enhance NK cell anti-tumor effects in hepatocellular carcinoma, Cancer Lett, 2015.

J. Zhu, S. He, J. Du, Z. Wang, W. Li et al., , 2015.

S. Zilio and P. Serafini, Neutrophils and Granulocytic MDSC: The Janus God of Cancer Immunotherapy, 2016.

J. R. Zucali, C. A. Dinarello, D. J. Oblon, M. A. Gross, L. Anderson et al.,

, Interleukin 1 stimulates fibroblasts to produce granulocyte-macrophage colonystimulating activity and prostaglandin E2, J. Clin. Invest, vol.77, pp.1857-1863

, Institut National Du Cancer -Accueil

D. Wang, M. Precopio, T. Lan, D. Yu, J. X. Tang et al., Antitumor activity and immune response induction of a dual agonist of Toll-like receptors 7 and 8, Mol Cancer Ther, vol.9, issue.6, pp.1788-97, 2010.

E. Koga-yamakawa, S. J. Dovedi, M. Murata, H. Matsui, A. J. Leishman et al., Intratracheal and oral administration of SM-276001: a selective TLR7 agonist, leads to antitumor efficacy in primary and metastatic models of cancer, Int J Cancer J Int Cancer, vol.132, issue.3, pp.580-90, 2013.

L. Mercier, I. Poujol, D. Sanlaville, A. Sisirak, V. Gobert et al., Tumor promotion by intratumoral plasmacytoid dendritic cells is reversed by TLR7 ligand treatment, Cancer Res, vol.73, issue.15, pp.4629-4669, 2013.

,

C. Serra-guill-en, E. Nagore, L. Hueso, V. Traves, F. Messeguer et al., A randomized pilot comparative study of topical methyl aminolevulinate photodynamic therapy versus imiquimod 5% versus sequential application of both therapies in immunocompetent patients with actinic keratosis: clinical and histologic outcomes, J Am Acad Dermatol, vol.66, issue.4, pp.131-138, 2012.

R. Narayan, H. Nguyen, J. J. Bentow, L. Moy, D. K. Lee et al., Immunomodulation by imiquimod in patients with high-risk primary melanoma, J Invest Dermatol, vol.132, issue.1, pp.163-172, 2012.

J. Cherfils-vicini, S. Platonova, M. Gillard, L. Laurans, P. Validire et al., Triggering of TLR7 and TLR8 expressed by human lung cancer cells induces cell survival and chemoresistance, J Clin Invest, vol.120, issue.4, pp.1285-97, 2010.

S. Chatterjee, L. Crozet, D. Damotte, K. Iribarren, C. Schramm et al., TLR7 promotes tumor progression, chemotherapy resistance, and poor clinical outcomes in non-small cell lung cancer, Cancer Res, vol.74, issue.18, p.25074614, 2014.

,

A. Ochi, C. S. Graffeo, C. P. Zambirinis, A. Rehman, M. Hackman et al., Toll-like receptor 7 regulates pancreatic carcinogenesis in mice and humans, J Clin Invest, vol.122, issue.11, pp.4118-4147, 2012.

F. E. Mohamed, R. M. Al-jehani, S. S. Minogue, F. Andreola, A. Winstanley et al., Effect of tolllike receptor 7 and 9 targeted therapy to prevent the development of hepatocellular carcinoma, Liver Int Off J Int Assoc Study Liver, 2014.

M. G. Kelly, A. B. Alvero, R. Chen, D. Silasi, V. M. Abrahams et al., TLR-4 signaling promotes tumor growth and paclitaxel chemoresistance in ovarian cancer, Cancer Res, vol.66, issue.7, pp.3859-68, 2006.

, 1. Anti-and pro-tumoral effects of TLR stimulation (Table 2)

.. .. ,

.. .. ,

.. .. ,

.. .. ,

.. .. ,

.. .. ,

.. .. Acknowledgments,

;. Adams and . Basith, Muccioli and Benencia, p.10, 2002.

. Eosinophils and . Grimm, Huen and Rook, 2002.

, pDC, plasmacytoid dendritic cells; cDC, conventional dendritic cells; NK, natural killer

. Tregs,

. Shi, Two studies of intestinal carcinoma reported that TLR2 had proor anti-tumoral effects. The first, favoring an anti-tumoral role of TLR2, demonstrated increased tumor progression and increased pro-inflammatory cytokines in a TLR2-KO mouse model of carcinogenesis created by dextran sulfate sodium, However, these studies were not based on the same tumor models, 2007.

S. Adams, Toll-like receptor agonists in cancer therapy, Immunotherapy, vol.1, pp.949-964, 2009.

A. Ahmed, J. H. Wang, and H. P. Redmond, Silencing of TLR4 increases tumor progression and lung metastasis in a murine model of breast cancer, Ann. Surg. Oncol, vol.20, pp.389-396, 2013.

S. Akira, S. Uematsu, and O. Takeuchi, Pathogen recognition and innate immunity, Cell, vol.124, pp.783-801, 2006.

L. Apetoh, F. Ghiringhelli, A. Tesniere, M. Obeid, C. Ortiz et al., Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy, Nat. Med, vol.13, pp.1050-1059, 2007.
URL : https://hal.archives-ouvertes.fr/hal-00316924

C. Aspord, L. Tramcourt, C. Leloup, J. Molens, M. Leccia et al., Imiquimod inhibits melanoma development by promoting pDC cytotoxic functions and impeding tumor vascularization, J. Invest. Dermatol, vol.134, pp.2551-2561, 2014.

F. Balkwill and L. M. Coussens, Cancer: an inflammatory link, Nature, vol.431, pp.405-406, 2004.

F. Balkwill and A. Mantovani, Inflammation and cancer: back to Virchow?, Lancet Lond. Engl, vol.357, pp.539-545, 2001.

S. Basith, B. Manavalan, G. Lee, S. G. Kim, and S. Choi, Toll-like receptor modulators: a patent review, Expert Opin. Ther. Pat, vol.21, pp.927-944, 2006.

S. Basith, B. Manavalan, T. H. Yoo, S. G. Kim, and S. Choi, Roles of Toll-like receptors in cancer: a double-edged sword for defense and offense, Arch. Pharm. Res, vol.35, pp.1297-1316, 2012.

A. K. Bauer, D. Dixon, L. M. Degraff, H. Cho, C. R. Walker et al., Toll-like receptor 4 in butylated hydroxytoluene-induced mouse pulmonary inflammation and tumorigenesis, 2005.

, J. Natl. Cancer Inst, vol.97, pp.1778-1781

A. A. Beg, Endogenous ligands of Toll-like receptors: implications for regulating inflammatory and immune responses, Trends Immunol, vol.23, pp.509-512, 2002.

L. Belmont, N. Rabbe, M. Antoine, D. Cathelin, C. Guignabert et al., Expression of TLR9 in tumor-infiltrating mononuclear cells enhances angiogenesis and is associated with a worse survival in lung cancer, Int. J. Cancer J. Int. Cancer, vol.134, pp.765-777, 2014.

R. Berger, H. Fiegl, G. Goebel, P. Obexer, M. Ausserlechner et al., Toll-like receptor 9 expression in breast and ovarian cancer is associated with poorly differentiated tumors, Cancer Sci, vol.101, pp.1059-1066, 2010.

M. E. Bianchi, DAMPs, PAMPs and alarmins: all we need to know about danger, J. Leukoc. Biol, vol.81, pp.1-5, 2007.

C. Brignole, D. Marimpietri, D. Di-paolo, P. Perri, F. Morandi et al., Therapeutic targeting of TLR9 inhibits cell growth and induces apoptosis in neuroblastoma, Cancer Res, vol.70, pp.9816-9826, 2010.

L. G. Burdelya, A. S. Gleiberman, I. Toshkov, S. Aygun-sunar, M. Bapardekar et al., Toll-like receptor 5 agonist protects mice from dermatitis and oral mucositis caused by local radiation: implications for head-and-neck cancer radiotherapy, Int. J. Radiat. Oncol. Biol. Phys, vol.83, pp.228-234, 2012.

Z. Cai, A. Sanchez, Z. Shi, T. Zhang, M. Liu et al., Activation of Toll-like receptor 5 on breast cancer cells by flagellin suppresses cell proliferation and tumor growth, Cancer Res, vol.71, pp.2466-2475, 2011.

R. Cammarota, V. Bertolini, G. Pennesi, E. O. Bucci, O. Gottardi et al., The tumor microenvironment of colorectal cancer: stromal TLR-4 expression as a potential prognostic marker, Pattern-recognition receptors and gastric cancer. Front. Immunol, vol.8, p.336, 2010.

S. Chatterjee, L. Crozet, D. Damotte, K. Iribarren, C. Schramm et al., TLR7 promotes tumor progression, chemotherapy resistance, and poor clinical outcomes in non-small cell lung cancer, Cancer Res, vol.74, pp.5008-5018, 2014.

R. Chen, A. B. Alvero, D. Silasi, and G. Mor, Inflammation, cancer and chemoresistance: taking advantage of the Toll-like receptor signaling pathway, Am. J. Reprod. Immunol. N. Y, vol.198, issue.57, pp.93-107, 2007.

X. Chen, F. Zhao, H. Zhang, Y. Zhu, K. Wu et al., Significance of TLR4/MyD88 expression in breast cancer, Int. J. Clin. Exp. Pathol, vol.8, pp.7034-7039, 2015.

J. Cherfils-vicini, S. Platonova, M. Gillard, L. Laurans, P. Validire et al., Triggering of TLR7 and TLR8 expressed by human lung cancer cells induces cell survival and chemoresistance, J. Clin. Invest, vol.120, pp.1285-1297, 2010.

V. Chew, C. Tow, C. Huang, E. Bard-chapeau, N. G. Copeland et al., , 2012.

, J. Natl. Cancer Inst, vol.104, pp.1796-1807

M. R. Chicoine, M. Zahner, E. K. Won, R. R. Kalra, T. Kitamura et al., The in vivo antitumoral effects of lipopolysaccharide against glioblastoma multiforme are mediated in part by Toll-like receptor 4, Neurosurgery, vol.60, pp.372-380, 2007.

A. I. Chin, A. K. Miyahira, A. Covarrubias, J. Teague, B. Guo et al., Toll-like receptor 3-mediated suppression of TRAMP prostate cancer shows the critical role of type I interferons in tumor immune surveillance, Cancer Res, vol.70, pp.2595-2603, 2010.

L. M. Coussens and Z. Werb, Inflammation and cancer, Nature, vol.420, pp.860-867, 2002.

C. D'agostini, F. Pica, G. Febbraro, S. Grelli, C. Chiavaroli et al., Antitumour effect of OM-174 and cyclophosphamide on murine B16 melanoma in different experimental conditions, Int. Immunopharmacol, vol.5, pp.1205-1212, 2005.

M. Dajon, K. Iribarren, I. Cremer, D. H. Dapito, A. Mencin et al., Dual roles of TLR7 in the lung cancer microenvironment. Oncoimmunology 4, e991615, Cancer Cell, vol.21, pp.504-516, 2012.

M. De-cesare, C. Calcaterra, G. Pratesi, L. Gatti, F. Zunino et al., Eradication of ovarian tumor xenografts by locoregional administration of targeted immunotherapy, Clin. Cancer Res, vol.14, pp.5512-5518, 2008.

G. Dranoff, Coordinated tumor immunity, J. Clin. Invest, vol.111, pp.1116-1118, 2003.

D. Droemann, D. Albrecht, J. Gerdes, A. J. Ulmer, D. Branscheid et al., Human lung cancer cells express functionally active Toll-like receptor 9, Respir. Res, vol.6, p.1, 2005.

G. P. Dunn, L. J. Old, and R. D. Schreiber, The three Es of cancer immunoediting, Annu. Rev. Immunol, vol.22, pp.329-360, 2004.

A. El-andaloussi, A. M. Sonabend, Y. Han, and M. S. Lesniak, Stimulation of TLR9 with CpG ODN enhances apoptosis of glioma and prolongs the survival of mice with experimental brain tumors, Glia, vol.54, pp.526-535, 2006.

L. Farnebo, A. Shahangian, Y. Lee, J. H. Shin, F. A. Scheeren et al., Targeting Toll-like receptor 2 inhibits growth of head and neck squamous cell carcinoma, Oncotarget, vol.6, pp.9897-9907, 2015.

B. Fernandez-garcia, N. Eiró, S. González-reyes, L. González, A. Aguirre et al., Clinical significance of Toll-like receptor 3, 4, and 9 in gastric cancer, J. Immunother. Hagerstown Md, issue.37, pp.77-83, 1997.

R. T. Figueiredo, P. L. Fernandez, D. S. Mourao-sa, B. N. Porto, F. F. Dutra et al., Characterization of heme as activator of Toll-like receptor 4, J. Biol. Chem, vol.282, pp.20221-20229, 2007.

W. H. Fridman, F. Pagès, C. Sautès-fridman, and J. Galon, The immune contexture in human tumours: impact on clinical outcome, Nat. Rev. Cancer, vol.12, pp.298-306, 2012.

M. Fukata, A. Chen, A. S. Vamadevan, J. Cohen, K. Breglio et al., Toll-like receptor-4 promotes the development of colitis-associated colorectal tumors, Gastroenterology, vol.133, pp.1869-1881, 2007.

G. Gambara, M. Desideri, A. Stoppacciaro, F. Padula, P. De-cesaris et al., TLR3 engagement induces IRF-3-dependent apoptosis in androgen-sensitive prostate cancer cells and inhibits tumour growth in vivo, J. Cell. Mol. Med, vol.19, pp.327-339, 2015.

D. Geng, S. Kaczanowska, A. Tsai, K. Younger, A. Ochoa et al., TLR5 ligand-secreting t cells reshape the tumor microenvironment and enhance antitumor activity, Cancer Res, vol.75, pp.1959-1971, 2015.

J. A. Gershan, K. M. Barr, J. J. Weber, W. Jing, B. D. Johnson et al., Immune modulating effects of cyclophosphamide and treatment with tumor lysate/CpG synergize to eliminate murine neuroblastoma, Cancer Immunol. Immunother. CII, vol.3, pp.217-226, 2011.

F. R. Greten, L. Eckmann, T. F. Greten, J. M. Park, Z. Li et al., IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer, Cell, vol.118, pp.285-296, 2004.

M. Grimm, M. Kim, A. Rosenwald, U. Heemann, C. Germer et al., Toll-like receptor (TLR) 7 and TLR8 expression on CD133+ cells in colorectal cancer points to a specific role for inflammation-induced TLRs in tumourigenesis and tumour progression, Eur. J. Cancer Oxf. Engl, issue.46, pp.2849-2857, 1990.

T. Grimmig, N. Matthes, K. Hoeland, S. Tripathi, A. Chandraker et al., TLR7 and TLR8 expression increases tumor cell proliferation and promotes chemoresistance in human pancreatic cancer, Int. J. Oncol, vol.47, pp.857-866, 2015.

J. Gu, R. Sun, S. Shen, and Z. Yu, The influence of TLR4 agonist lipopolysaccharides on hepatocellular carcinoma cells and the feasibility of its application in treating liver cancer, OncoTargets Ther, vol.8, pp.2215-2225, 2015.

D. Hanahan and R. A. Weinberg, The hallmarks of cancer, Cell, vol.100, pp.57-70, 2000.

D. Hanahan and R. A. Weinberg, Hallmarks of cancer: the next generation, Cell, vol.144, pp.646-674, 2011.

U. Hasan, C. Chaffois, C. Gaillard, V. Saulnier, E. Merck et al., Human TLR10 is a functional receptor, expressed by B cells and plasmacytoid dendritic cells, which activates gene transcription through MyD88, J. Immunol. Baltim. Md, vol.1950, issue.174, pp.2942-2950, 2005.

M. Hausmann, S. Kiessling, S. Mestermann, G. Webb, T. Spöttl et al., Toll-like receptors 2 and 4 are up-regulated during intestinal inflammation, Gastroenterology, vol.122, 1987.

W. He, Q. Liu, L. Wang, W. Chen, N. Li et al., TLR4 signaling promotes immune escape of human lung cancer cells by inducing immunosuppressive cytokines and apoptosis resistance, Mol. Immunol, vol.44, pp.2850-2859, 2007.

C. J. Hertz, Q. Wu, E. M. Porter, Y. J. Zhang, K. Weismüller et al., Activation of Toll-like receptor 2 on human tracheobronchial epithelial cells induces the antimicrobial peptide human beta defensin-2, J. Immunol. Baltim. Md, vol.1950, issue.171, pp.6820-6826, 2003.

V. Ho, T. S. Lim, J. Lee, J. Steinberg, R. Szmyd et al., TLR3 agonist and Sorafenib combinatorial therapy promotes immune activation and controls hepatocellular carcinoma progression, Oncotarget, 2015.

P. A. Hopkins and S. Sriskandan, Mammalian Toll-like receptors: to immunity and beyond, Clin. Exp. Immunol, vol.140, pp.395-407, 2005.

M. W. Hornef, B. H. Normark, A. Vandewalle, and S. Normark, Intracellular recognition of lipopolysaccharide by Toll-like receptor 4 in intestinal epithelial cells, J. Exp. Med, vol.198, pp.1225-1235, 2003.

V. Hornung, S. Rothenfusser, S. Britsch, A. Krug, B. Jahrsdörfer et al., Quantitative expression of Toll-like receptor 1-10 mRNA in cellular subsets of human peripheral blood mononuclear cells and sensitivity to CpG oligodeoxynucleotides, J. Immunol. Baltim. Md, vol.1950, issue.168, pp.4531-4537, 2002.

C. Hsiao, P. Chen, C. Cheng, M. Tsai, C. Chang et al., Toll-like receptor-4 is a target for suppression of proliferation and chemoresistance in HepG2 hepatoblastoma cells, Cancer Lett, vol.368, pp.144-152, 2015.

B. Huang, J. Zhao, H. Li, K. He, Y. Chen et al., Toll-like receptors on tumor cells facilitate evasion of immune surveillance, Cancer Res, vol.65, pp.5009-5014, 2005.

B. Huang, J. Zhao, S. Shen, H. Li, K. He et al., Listeria monocytogenes promotes tumor growth via tumor cell Toll-like receptor 2 signaling, Cancer Res, vol.67, pp.4346-4352, 2007.

A. O. Huen and A. H. Rook, Toll receptor agonist therapy of skin cancer and cutaneous T-cell lymphoma, Curr. Opin. Oncol, vol.26, pp.237-244, 2014.

N. Husseinzadeh and S. M. Davenport, Role of Toll-like receptors in cervical, endometrial and ovarian cancers: a review, Gynecol. Oncol, vol.135, pp.359-363, 2014.

B. Jahrsdörfer, J. E. Wooldridge, S. E. Blackwell, C. M. Taylor, T. S. Griffith et al., Immunostimulatory oligodeoxynucleotides induce apoptosis of B cell chronic lymphocytic leukemia cells, J. Leukoc. Biol, vol.77, pp.378-387, 2005.

S. Jain, S. Suklabaidya, B. Das, S. K. Raghav, S. K. Batra et al., TLR4 activation by lipopolysaccharide confers survival advantage to growth factor deprived prostate cancer cells, The Prostate, vol.75, pp.1020-1033, 2015.

C. A. Janeway and R. Medzhitov, Innate immune recognition, Annu. Rev. Immunol, vol.20, pp.197-216, 2002.

G. Jego, R. Bataille, A. Geffroy-luseau, G. Descamps, and C. Pellat-deceunynck, Pathogen-associated molecular patterns are growth and survival factors for human myeloma cells through Toll-like receptors, Leukemia, vol.20, pp.1130-1137, 2006.

Q. Jiang, H. Wei, and Z. Tian, Poly I:C enhances cycloheximide-induced apoptosis of tumor cells through TLR3 pathway, BMC Cancer, vol.8, p.12, 2008.

K. Karikó, H. Ni, J. Capodici, M. Lamphier, and D. Weissman, mRNA is an endogenous ligand for Toll-like receptor 3, J. Biol. Chem, vol.279, pp.12542-12550, 2004.

M. Karin, Nuclear factor-kappaB in cancer development and progression, Nature, vol.441, pp.431-436, 2006.

T. Kawai and S. Akira, The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors, Nat. Immunol, vol.11, pp.373-384, 2010.

M. G. Kelly, A. B. Alvero, R. Chen, D. Silasi, V. M. Abrahams et al., TLR-4 signaling promotes tumor growth and paclitaxel chemoresistance in ovarian cancer, Cancer Res, vol.66, pp.3859-3868, 2006.

S. D. Kundu, C. Lee, B. K. Billips, G. M. Habermacher, Q. Zhang et al., The Toll-like receptor pathway: a novel mechanism of infection-induced carcinogenesis of prostate epithelial cells, The Prostate, vol.68, pp.223-229, 2008.

L. Mercier, I. Poujol, D. Sanlaville, A. Sisirak, V. Gobert et al., Tumor promotion by intratumoral plasmacytoid dendritic cells is reversed by TLR7 ligand treatment, Cancer Res, vol.73, pp.4629-4640, 2013.

N. D. Leigh, G. Bian, X. Ding, H. Liu, S. Aygun-sunar et al., A flagellin-derived Toll-like receptor 5 agonist stimulates cytotoxic lymphocyte-mediated tumor immunity, PLoS One, vol.9, p.85587, 2014.

B. Lemaitre, E. Nicolas, L. Michaut, J. M. Reichhart, and J. A. Hoffmann, The dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults, Cell, vol.86, pp.973-983, 1996.

S. Li, R. Sun, Y. Chen, H. Wei, and Z. Tian, TLR2 limits development of hepatocellular carcinoma by reducing IL18-mediated immunosuppression, Cancer Res, vol.75, pp.986-995, 2015.

Y. Li, Y. Shi, L. Mccaw, Y. Li, F. Zhu et al., Microenvironmental interleukin-6 suppresses Toll-like receptor signaling in human leukemia cells through miR-17/19A, Blood, vol.126, pp.766-778, 2015.

H. Lin, J. Yan, Z. Wang, F. Hua, J. Yu et al., Loss of immunity-supported senescence enhances susceptibility to hepatocellular carcinogenesis and progression in Toll-like receptor 2-deficient mice, Hepatol. Baltim. Md, vol.57, pp.171-182, 2013.

Y. Liu, W. Yan, S. Tohme, M. Chen, Y. Fu et al., Hypoxia induced HMGB1 and mitochondrial DNA interactions mediate tumor growth in hepatocellular carcinoma through Toll-like receptor 9, J. Hepatol, vol.63, pp.114-121, 2015.

M. Lohs-schardin, C. Cremer, and C. Nüsslein-volhard, A fate map for the larval epidermis of Drosophila melanogaster: localized cuticle defects following irradiation of the blastoderm with an ultraviolet laser microbeam, Dev. Biol, vol.73, pp.239-255, 1979.

E. L. Lowe, T. R. Crother, S. Rabizadeh, B. Hu, H. Wang et al., Toll-like receptor 2 signaling protects mice from tumor development in a mouse model of colitis-induced cancer, Oncotarget, vol.5, pp.22564-22574, 2010.

F. Ma, Z. Liu, X. Hu, H. Ling, S. Li et al., Prognostic value of myeloid differentiation primary response 88 and Toll-like receptor 4 in breast cancer patients, PLoS One, vol.9, p.111639, 2014.

C. W. Mai, Y. B. Kang, and M. R. Pichika, Should a Toll-like receptor 4 (TLR-4) agonist or antagonist be designed to treat cancer? TLR-4: its expression and effects in the ten most common cancers, OncoTargets Ther, vol.6, pp.1573-1587, 2013.

M. U. Martin and H. Wesche, Summary and comparison of the signaling mechanisms of the toll/interleukin-1 receptor family, Biochim. Biophys. Acta, vol.1592, pp.265-280, 2002.

A. Maruyama, H. Shime, Y. Takeda, M. Azuma, M. Matsumoto et al., Pam2 lipopeptides systemically increase myeloid-derived suppressor cells through TLR2 signaling, Biochem. Biophys. Res. Commun, vol.457, pp.445-450, 2015.

T. Matijevic, M. Marjanovic, and J. Pavelic, Functionally active Toll-like receptor 3 on human primary and metastatic cancer cells, Scand. J. Immunol, vol.70, pp.18-24, 2009.

R. Medzhitov, P. Preston-hurlburt, and C. A. Janeway, A human homologue of the Drosophila Toll protein signals activation of adaptive immunity, Nature, vol.388, pp.394-397, 1997.

R. Medzhitov, P. Preston-hurlburt, E. Kopp, A. Stadlen, C. Chen et al., MyD88 is an adaptor protein in the hToll/IL-1 receptor family signaling pathways, Mol. Cell, vol.2, pp.253-258, 1998.

M. Molteni, D. Marabella, C. Orlandi, and C. Rossetti, Melanoma cell lines are responsive in vitro to lipopolysaccharide and express TLR-4, Cancer Lett, vol.235, pp.75-83, 2006.

D. Moreira, Q. Zhang, D. M. Hossain, S. Nechaev, H. Li et al., TLR9 signaling through NF-(B/RELA and STAT3 promotes tumor-propagating potential of prostate cancer cells, Oncotarget, vol.6, pp.17302-17313, 2015.

M. Muccioli and F. Benencia, Toll-like receptors in ovarian cancer as targets for immunotherapies, Front. Immunol, vol.5, p.341, 2014.

A. Muir, G. Soong, S. Sokol, B. Reddy, M. I. Gomez et al., Toll-like receptors in normal and cystic fibrosis airway epithelial cells, Am. J. Respir. Cell Mol. Biol, vol.30, pp.777-783, 2004.

H. Nagase, S. Okugawa, Y. Ota, M. Yamaguchi, H. Tomizawa et al., Expression and function of Toll-like receptors in eosinophils: activation by Toll-like receptor 7 ligand, J. Immunol. Baltim. Md, vol.195, issue.171, pp.3977-3982, 2003.

M. Naseemuddin, A. Iqbal, T. H. Nasti, J. L. Ghandhi, A. D. Kapadia et al., Cell mediated immune responses through TLR4 prevents DMBA-induced mammary carcinogenesis in mice, Int. J. Cancer J. Int. Cancer, vol.130, pp.765-774, 2012.

K. Newton and V. M. Dixit, Signaling in innate immunity and inflammation, Cold Spring Harb. Perspect. Biol, vol.4, 2012.

N. Nomi, S. Kodama, and M. Suzuki, Toll-like receptor 3 signaling induces apoptosis in human head and neck cancer via survivin associated pathway, Oncol. Rep, vol.24, pp.225-231, 2010.

A. Ochi, C. S. Graffeo, C. P. Zambirinis, A. Rehman, M. Hackman et al., Toll-like receptor 7 regulates pancreatic carcinogenesis in mice and humans, J. Clin. Invest, vol.122, pp.4118-4129, 2012.

M. Okamoto, T. Oshikawa, T. Tano, G. Ohe, S. Furuichi et al., Involvement of Toll-like receptor 4 signaling in interferon-gamma production and antitumor effect by streptococcal agent OK-432, J. Natl. Cancer Inst, vol.95, pp.316-326, 2003.

M. Oosting, S. Cheng, J. M. Bolscher, R. Vestering-stenger, T. S. Plantinga et al., Human TLR10 is an anti-inflammatory pattern-recognition receptor, 2014.

, Proc. Natl. Acad. Sci. U. S. A, vol.111, pp.4478-4484

F. Pagès, J. Galon, M. Dieu-nosjean, E. Tartour, C. Sautès-fridman et al., Immune infiltration in human tumors: a prognostic factor that should not be ignored, Oncogene, vol.29, pp.1093-1102, 2010.

S. Pandey and D. K. Agrawal, Immunobiology of Toll-like receptors: emerging trends, Immunol. Cell Biol, vol.84, pp.333-341, 2006.

A. Paone, D. Starace, R. Galli, F. Padula, P. De-cesaris et al., Toll-like receptor 3 triggers apoptosis of human prostate cancer cells through a PKC-alpha-dependent mechanism, Carcinogenesis, vol.29, pp.1334-1342, 2008.

J. Park, H. Yoon, D. Kim, S. Kim, S. Ahn et al., Toll-like receptor 5 activation promotes migration and invasion of salivary gland adenocarcinoma, J. Oral Pathol. Med, vol.40, pp.187-193, 2011.

A. M. Piccinini, K. S. Midwood, E. Pikarsky, R. M. Porat, I. Stein et al., NF-kappaB functions as a tumour promoter in inflammation-associated cancer, Mediators Inflamm, vol.431, pp.461-466, 2004.

P. Pimentel-nunes, L. Afonso, P. Lopes, R. Roncon-albuquerque, N. Gonç-alves et al., Increased expression of Toll-like receptors (TLR) 2, 4 and 5 in gastric dysplasia, 2011.

, Pathol. Oncol. Res. POR, vol.17, pp.677-683

J. Pradere, D. H. Dapito, and R. F. Schwabe, The yin and yang of toll-like receptors in cancer, Oncogene, vol.33, pp.3485-3495, 2014.

S. H. Rhee, E. Im, and C. Pothoulakis, Toll-like receptor 5 engagement modulates tumor development and growth in a mouse xenograft model of human colon cancer, Gastroenterology, vol.135, pp.518-528, 2008.

F. L. Rock, G. Hardiman, J. C. Timans, R. A. Kastelein, and J. F. Bazan, A family of human receptors structurally related to Drosophila Toll, Proc. Natl. Acad. Sci. U. S. A, vol.95, pp.588-593, 1998.

H. Ronkainen, P. Hirvikoski, S. Kauppila, K. S. Vuopala, T. K. Paavonen et al., Absent toll-like receptor-9 expression predicts poor prognosis in renal cell carcinoma, J. Exp. Clin. Cancer Res. CR, vol.30, p.84, 2011.

M. R. Rutkowski, T. L. Stephen, N. Svoronos, M. J. Allegrezza, A. J. Tesone et al., Microbially driven TLR5-dependent signaling governs distal malignant progression through tumor-promoting inflammation, Cancer Cell, vol.27, pp.27-40, 2015.

B. Salaun, S. Lebecque, S. Matikainen, D. Rimoldi, and P. Romero, Toll-like receptor 3 expressed by melanoma cells as a target for therapy?, Clin. Cancer Res, vol.13, pp.4565-4574, 2007.

T. Sato, T. Shimosato, A. Ueda, Y. Ishigatsubo, and D. M. Klinman, Intrapulmonary delivery of CpG microparticles eliminates lung tumors, Mol. Cancer Ther, vol.14, pp.2198-2205, 2015.

F. A. Scheeren, A. H. Kuo, L. J. Van-weele, S. Cai, I. Glykofridis et al., A cell-intrinsic role for TLR2-MYD88 in intestinal and breast epithelia and oncogenesis, Nat. Cell Biol, vol.16, pp.1238-1248, 2014.

B. Schmausser, M. Andrulis, S. Endrich, H. Müller-hermelink, and M. Eck, Toll-like receptors TLR4, TLR5 and TLR9 on gastric carcinoma cells: an implication for interaction with Helicobacter pylori, Int. J. Med. Microbiol. IJMM, vol.295, pp.179-185, 2005.

V. Shankaran, H. Ikeda, A. T. Bruce, J. M. White, P. E. Swanson et al., IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity, Nature, vol.410, pp.1107-1111, 2001.

W. Shi, L. Su, Q. Li, L. Sun, J. Lv et al., Suppression of Toll-like receptor 2 expression inhibits the bioactivity of human hepatocellular carcinoma, Tumour Biol, vol.35, pp.9627-9637, 2014.

H. Shime, M. Matsumoto, H. Oshiumi, S. Tanaka, A. Nakane et al., Toll-like receptor 3 signaling converts tumor-supporting myeloid cells to tumoricidal effectors, Proc. Natl. Acad. Sci. U. S. A, vol.109, pp.2066-2071, 2012.

H. Shojaei, H. Oberg, M. Juricke, L. Marischen, M. Kunz et al., Toll-like receptors 3 and 7 agonists enhance tumor cell lysis by human gammadelta T cells, Cancer Res, vol.69, pp.8710-8717, 2009.

E. Song, M. Kang, Y. Kim, S. Kim, S. Lee et al., Flagellin promotes the proliferation of gastric cancer cells via the Toll-like receptor 5, Int. J. Mol. Med, vol.28, pp.115-119, 2011.

D. E. Spaner, Y. Shi, D. White, J. Mena, C. Hammond et al., Immunomodulatory effects of Toll-like receptor-7 activation on chronic lymphocytic leukemia cells, Leukemia, vol.20, pp.286-295, 2006.

D. E. Spaner, Y. Shi, D. White, S. Shaha, L. He et al., A phase I/II trial of TLR-7 agonist immunotherapy in chronic lymphocytic leukemia, Leukemia, vol.24, pp.222-226, 2010.

M. Szczepa?ski, M. Stelmachowska, L. Stryczy?ski, W. Golusi?ski, H. Samara et al., Assessment of expression of Toll-like receptors 2, 3 and 4 in laryngeal carcinoma, Eur. Arch. Oto-Rhino-Laryngol, vol.264, pp.525-530, 2007.

M. J. Szczepanski, M. Czystowska, M. Szajnik, M. Harasymczuk, M. Boyiadzis et al., Triggering of Toll-like receptor 4 expressed on human head and neck squamous cell carcinoma promotes tumor development and protects the tumor from immune attack, Cancer Res, vol.69, pp.3105-3113, 2009.

R. Takemura, H. Takaki, S. Okada, H. Shime, T. Akazawa et al., PolyI:C-induced, TLR3/RIP3-dependent necroptosis backs up immune effector-Mediated tumor elimination in vivo, Cancer Immunol. Res, vol.3, pp.902-914, 2015.

G. E. Theodoropoulos, V. Saridakis, T. Karantanos, N. V. Michalopoulos, F. Zagouri et al., Toll-like receptors gene polymorphisms may confer increased susceptibility to breast cancer development, Breast Edinb. Scotl, vol.21, pp.534-538, 2012.

G. Trinchieri, Cancer and inflammation: an old intuition with rapidly evolving new concepts, Annu. Rev. Immunol, vol.30, pp.677-706, 2012.

H. Tye, C. L. Kennedy, M. Najdovska, L. Mcleod, W. Mccormack et al., , 2012.

E. Vacchelli, A. Eggermont, C. Sautès-fridman, J. Galon, L. Zitvogel et al., Immune stimulation mediated by autoantigen binding sites within small nuclear RNAs involves Toll-like receptors 7 and 8, J. Exp. Med, vol.202, pp.1575-1585, 2005.

C. Wang, S. Cao, Y. Yan, Q. Ying, T. Jiang et al., TLR9 expression in glioma tissues correlated to glioma progression and the prognosis of GBM patients, BMC Cancer, vol.10, p.415, 2010.

J. Wang, Y. Zhang, X. Wei, J. Li, X. Nan et al., Circulating toll-like receptor (TLR) 2, TLR4, and regulatory T cells in patients with chronic hepatitis C, APMIS acta pathol. Microbiol. Immunol. Scand, vol.118, pp.261-270, 2010.

Z. Wang, J. Yan, H. Lin, F. Hua, X. Wang et al., Toll-like receptor 4 activity protects against hepatocellular tumorigenesis and progression by regulating expression of DNA repair protein Ku70 in mice, Hepatol. Baltim. Md, vol.57, pp.1869-1881, 2013.

W. Xie, Y. Wang, Y. Huang, H. Yang, J. Wang et al., Toll-like receptor 2 mediates invasion via activating NF-kappaB in MDA-MB-231 breast cancer cells, Biochem. Biophys. Res. Commun, vol.379, pp.1027-1032, 2009.

Y. Xu, L. Chen, J. Zhou, Y. Wu, and Y. Zhu, Inhibitory effect of dsRNA TLR3 agonist in a rat hepatocellular carcinoma model, Mol. Med. Rep, vol.8, pp.1037-1042, 2013.

Y. Xu, L. Chen, G. Wang, J. Zhou, Y. Zhang et al., A synthetic dsRNA, as a TLR3 pathwaysynergist, combined with sorafenib suppresses HCC in vitro and in vivo, BMC Cancer, vol.13, p.527, 2013.

H. Yang, H. Zhou, P. Feng, X. Zhou, H. Wen et al., Reduced expression of Toll-like receptor 4 inhibits human breast cancer cells proliferation and inflammatory cytokines secretion, J. Exp. Clin. Cancer Res. CR, vol.29, p.92, 2010.

H. Yang, B. Wang, T. Wang, L. Xu, C. He et al., Dual topology of functional Toll-like receptor 3 expression in human hepatocellular carcinoma: differential signaling mechanisms of TLR3-induced NF-kappaB activation and apoptosis, Front. Immunol, vol.9, pp.929-936, 2008.

N. Yusuf, T. H. Nasti, J. A. Long, M. Naseemuddin, A. P. Lucas et al., Protective role of Toll-like receptor 4 during the initiation stage of cutaneous chemical carcinogenesis, Cancer Res, vol.68, pp.615-622, 2008.

C. P. Zambirinis, E. Levie, S. Nguy, A. Avanzi, R. Barilla et al., TLR9 ligation in pancreatic stellate cells promotes tumorigenesis, J. Exp. Med, vol.212, pp.2077-2094, 2015.

J. Zhang, H. Wu, L. Wang, Y. Tian, J. Zhang et al., Expression and significance of TLR4 and HIF-1alpha in pancreatic ductal adenocarcinoma, World J. Gastroenterol. WJG, vol.16, pp.2881-2888, 2010.

Y. Zhang, F. Luo, Y. Cai, N. Liu, L. Wang et al., TLR1/TLR2 agonist induces tumor regression by reciprocal modulation of effector and regulatory T cells, J. Immunol. Baltim. Md, vol.1950, issue.186, pp.1963-1969, 2011.

Y. Zhang, Q. Wang, A. Ma, Y. Li, R. Li et al., Functional expression of TLR9 in esophageal cancer, Oncol. Rep, vol.31, pp.2298-2304, 2014.

S. Zhou, F. Li, Y. Qiao, X. Zhang, and Z. Wang, Toll-like receptor 5 agonist inhibition of growth of A549 lung cancer cells in vivo in a Myd88 dependent manner. Asian Pac, J. Cancer Prev. APJCP, vol.13, pp.2807-2812, 2012.

H. Zhou, J. Chen, J. Hu, Y. Luo, F. Li et al., High expression of Toll-like receptor 5 correlates with better prognosis in non-small-cell lung cancer: an anti-tumor effect of TLR5 signaling in non-small cell lung cancer, J. Cancer Res. Clin. Oncol, vol.140, pp.633-643, 2014.

Z. Zhou, X. Yu, J. Zhang, Z. Tian, and C. Zhang, TLR7/8 agonists promote NK-DC cross-talk to enhance NK cell anti-tumor effects in hepatocellular carcinoma, Cancer Lett, vol.369, pp.298-306, 2015.

J. Zhu, S. He, J. Du, Z. Wang, W. Li et al., Local administration of a novel Toll-like receptor 7 agonist in combination with doxorubicin induces durable tumouricidal effects in a murine model of T cell lymphoma, J. Hematol. Oncol, vol.8, p.21, 2015.