The neuronal splicing factor Nova controls alternative splicing in N-type and P-type CaV2 calcium channels, 2010. ,
The PDL1-PD1 axis converts human T H1 cells into regulatory T cells, Sci. Transl. Med, vol.3, 2011. ,
High frequency of T cells specific for cryptic epitopes in melanoma patients, vol.2, p.25374, 2013. ,
Preferential role for NF-kappa B/Rel signaling in the type 1 but not type 2 T cell-dependent immune response in vivo, J. Immunol, vol.163, pp.5116-5124, 1999. ,
Limiting of the innate immune response by SF3A-dependent control of MyD88 alternative mRNA splicing, PLoS Genet, vol.9, p.1003855, 2013. ,
Transient activation of NF-?B through a TAK1/IKK kinase pathway by TGF-?1 inhibits AP-1/SMAD signaling and apoptosis: Implications in liver tumor formation, Oncogene, vol.22, pp.412-425, 2003. ,
The paradox of Th17 cell functions in tumor immunity, Cell. Immunol, vol.322, pp.15-25, 2017. ,
Epigenetics and T helper 1 differentiation, Immunology, 2009. ,
Alternative splicing as a regulator of development and tissue identity, Nat. Rev. Mol. Cell Biol, vol.18, pp.437-451, 2017. ,
Anti-tumor activity of splice-switching oligonucleotides, Nucleic Acids Res, vol.38, pp.8348-8356, 2010. ,
Help for cytotoxic-T-cell responses is mediated by CD4O signalling, Nature, 1998. ,
CD44 Staining of Cancer Stem-Like Cells Is Influenced by Down-Regulation of CD44 Variant Isoforms and Up-Regulation of the Standard CD44 Isoform in the Population of Cells That Have Undergone Epithelial-to-Mesenchymal Transition, PLoS One, vol.8, 2013. ,
CD8 lethargy in the absence of CD4 help, Eur. J. Immunol, vol.32, pp.2199-2207, 2002. ,
Tissue and cell-specific expression of the p53-target genes: bax, fas, mdm2 and waf1/p21, before and following ionising irradiation in mice, Oncogene, vol.19, pp.649-660, 2000. ,
Molecular interactions between interferon consensus sequence binding protein and members of the interferon regulatory factor family, Proc. Natl. Acad. Sci. U. S. A, vol.91, pp.5046-5050, 1994. ,
Transforming growth factor beta and cyclosporin A inhibit the inducible activity of the interleukin-2 gene in T cells through a noncanonical octamer-binding site, Mol. Cell. Biol, vol.13, pp.1155-1162, 2015. ,
Crohn's disease: Th1, Th17 or both? The change of a paradigm: new immunological and genetic insights implicate Th17 cells in the pathogenesis of Crohn's disease, Gut, vol.58, pp.1152-1167, 2009. ,
Induction of CD70 on dendritic cells through CD40 or TLR stimulation contributes to the development of CD8+ T cell responses in the absence of CD4+ T cells, J. Immunol, vol.174, pp.710-717, 2005. ,
Evolution of SR protein and hnRNP splicing regulatory factors, Wiley Interdiscip. Rev. RNA, 2012. ,
, , 2012.
TCF/LEFs and Wnt signaling in the nucleus, Cold Spring Harb. Perspect. Biol, vol.4, 2012. ,
Analysis of Major Histocompatibility Complex (MHC) Immunopeptidomes Using Mass Spectrometry, Mol. Cell. Proteomics, vol.14, pp.3105-3117, 2015. ,
Defective control of pre-messenger RNA splicing in human disease, J. Cell Biol, vol.212, pp.13-27, 2016. ,
SHP-1 and SHP-2 associate with immunoreceptor tyrosine-based switch motif of programmed death 1 upon primary human T cell stimulation, but only receptor ligation prevents T cell activation, J. Immunol, vol.173, pp.945-954, 2004. ,
Conversion of Peripheral CD4 + CD25 ? Naive T Cells to CD4 + CD25 + Regulatory T Cells by TGF-? Induction of Transcription Factor Foxp3, J. Exp. Med, vol.198, pp.1875-1886, 2003. ,
A Small Molecule Inhibitor of ITK and RLK Impairs Th1 Differentiation and Prevents Colitis Disease Progression, J. Immunol, 2015. ,
An amazing sequence arrangement at the 5' ends of adenovirus 2 messenger, RNA. Cell, vol.12, pp.1-8, 1977. ,
T lymphocyte subsets in cancer immunity: Friends or foes, J. Leukoc. Biol, vol.105, pp.243-255, 2019. ,
Protective CD8 memory T cell responses to mouse melanoma are generated in the absence of CD4 T cell help, PLoS One, vol.6, 2011. ,
Role of the Long Non-Coding RNA MAPT-AS1 in Regulation of Microtubule Associated Protein Tau (MAPT) Expression in Parkinson's Disease, PloS One, vol.11, issue.6, p.157924, 2016. ,
Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain, Nature, 2003. ,
Natural and adaptive foxp3+ regulatory T cells: more of the same or a division of labor?, Immunity, vol.30, pp.626-635, 2009. ,
Regulation of B-lymphocyte negative and positive selection by tyrosine phosphatase CD45, Nature, vol.381, pp.325-328, 1996. ,
, Death in T Cells via Downregulation of c-Myc, J. Exp. Med, vol.189, pp.231-239
IFN-?-Induced MHC Class II Expression: Transactivation of Class II Transactivator Promoter IV by IFN Regulatory Factor-1 is Regulated by Protein Kinase C-?, J. Immunol, 2003. ,
IFN-gamma-induced MHC class II expression: transactivation of class II transactivator promoter IV by IFN regulatory factor-1 is regulated by protein kinase C-alpha, J. Immunol, vol.171, pp.4187-4194, 2003. ,
Mechanism of Transforming Growth Factor ?-induced Inhibition of T Helper Type 1 Differentiation, J. Exp. Med, vol.195, pp.1499-1505, 2002. ,
Evidence that sequence-independent binding of highly conserved U2 snRNP proteins upstream of the branch site is required for assembly of spliceosomal complex A, Genes Dev, vol.10, pp.233-243, 1996. ,
Lack of IRF-1 expression in acute promyelocytic leukemia and in a subset of acute myeloid leukemias with del(5)(q31), Leukemia, vol.13, pp.1960-1971, 1999. ,
Positive regulatory role of IL-12 in macrophages and modulation by IFN-gamma, J. Immunol, vol.167, pp.221-227, 2001. ,
CXCR3 in T cell function, Exp. Cell Res, 2011. ,
Identification of Human Macrophage Inflammatory Proteins 1? and 1? as a Native Secreted Heterodimer, J. Biol. Chem, vol.28, pp.241-247, 2001. ,
Identification of new FOXP3 mutations and prenatal diagnosis of IPEX syndrome, Prenat. Diagn, vol.30, pp.1072-1078, 2010. ,
URL : https://hal.archives-ouvertes.fr/inserm-00588282
The Neurobiology of Multiple Sclerosis: Genes, Inflammation, and Neurodegeneration, 2006. ,
NEK7 is an essential mediator of NLRP3 activation downstream of potassium efflux, Nature, vol.530, pp.354-357, 2016. ,
T-bet Activates Th1 Genes through Mediator and the Super Elongation Complex, Cell Rep, 2016. ,
Phosphorylation-dependent regulation of PSF by GSK3 controls CD45 alternative splicing, Mol. Cell, vol.40, pp.126-137, 2010. ,
Critical roles of c-Rel in autoimmune inflammation and helper T cell differentiation, J. Clin. Invest, vol.110, pp.843-850, 2002. ,
Vascular endothelial growth factor and angiogenesis, Pharmacol. Rev, vol.56, pp.549-580, 2004. ,
TNF-in Cancer Treatment: Molecular Insights, Antitumor Effects, and Clinical Utility, Oncologist, 2006. ,
Alternative splicing regulates stochastic NLRP3 activity, Nat. Commun, vol.10, 2019. ,
CD4+ Th1 cells promote CD8+ Tc1 cell survival, memory response, tumor localization and therapy by targeted delivery of interleukin 2 via acquired pMHC I complexes, 2007. ,
2004 Huber, NF-?B is essential for epithelial, PDF, vol.114, pp.569-581, 2004. ,
IL-2 production in developing Th1 cells is regulated by heterodimerization of RelA and T-bet and requires T-bet serine residue 508, J. Exp. Med, 2005. ,
Cutting edge: naturally occurring soluble form of mouse Toll-like receptor 4 inhibits lipopolysaccharide signaling, J. Immunol, vol.165, pp.6682-6686, 2000. ,
The symphony of the ninth: the development and function of Th9 cells, Curr. Opin. Immunol, vol.24, pp.303-307, 2012. ,
Systematic Analysis of Splice-Site-Creating Mutations in, Cancer. Cell Rep, vol.23, pp.270-281, 2018. ,
The transcription factors T-bet and GATA-3 control alternative pathways of T-cell differentiation through a shared set of target genes, Proc. Natl. Acad. Sci, 2009. ,
Interferon gamma induced by resveratrol analog, HS-1793, reverses the properties of tumor associated macrophages, Int. Immunopharmacol, vol.22, pp.303-310, 2014. ,
Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation, Science, vol.325, pp.1006-1010, 2009. ,
The fundamental role of epigenetic events in cancer, Nat. Rev. Genet, vol.3, pp.415-428, 2002. ,
Thymic selection of CD4+CD25+ regulatory T cells induced by an agonist self-peptide, Nat. Immunol, vol.2, pp.301-306, 2001. ,
Comprehensive Analysis of Alternative Splicing Across Tumors from 8,705 Patients, Cancer Cell, vol.34, pp.211-224, 2018. ,
Tumour ischaemia by interferon-? resembles physiological blood vessel regression, Nature, 2017. ,
T-bet and GATA3 orchestrate Th1 and Th2 differentiation through lineage-specific targeting of distal regulatory elements, Nat. Commun, 2012. ,
The contribution of transcription factor IRF1 to the interferon?-interleukin 12 signaling axis and TH1 versus TH-17 differentiation of CD4+ T cells, Nat. Immunol, 2008. ,
The contribution of transcription factor IRF1 to the interferon?-interleukin 12 signaling axis and TH1 versus TH-17 differentiation of CD4+ T cells, Nat. Immunol, vol.9, pp.34-41, 2008. ,
Critical role of IRF1 and BATF in forming chromatin landscape during type 1 regulatory cell differentiation, Nat. Immunol, vol.18, pp.412-421, 2017. ,
RNA required for cardiovascular lineage commitment, 2013. ,
, Cell, vol.152, issue.3, pp.570-583, 2013.
Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF beta receptor for degradation, Mol. Cell, vol.6, pp.1365-1375, 2000. ,
Effects of interferon-gamma on secretion of vascular endothelial growth factor by endometrial stromal cells, Am. J. Reprod. Immunol, vol.43, pp.47-52, 2000. ,
Preferential recruitment of interferon-gamma-expressing TH17 cells in multiple sclerosis, Ann. Neurol, vol.66, pp.390-402, 2009. ,
Costimulatory ligand CD70 allows induction of CD8+ T-cell immunity by immature dendritic cells in a vaccination setting, Blood, 2009. ,
Multiple roles for CD4+ T cells in anti-tumor immune responses, Immunol. Rev, 2008. ,
Cotranscriptional splicing efficiency differs dramatically between Drosophila and mouse, RNA, vol.18, pp.2174-2186, 2012. ,
Functional dissection of the transactivation domain of interferon regulatory factor-1, Biochem. Biophys. Res. Commun, vol.304, pp.253-259, 2003. ,
, SRSF2 Mutations Contribute to Myelodysplasia by Mutant-Specific Effects on Exon Recognition, vol.27, pp.617-630, 2015.
IRF-1 expression induces apoptosis and inhibits tumor growth in mouse mammary cancer cells in vitro and in vivo, Oncogene, vol.23, pp.1125-1135, 2004. ,
In vivo formation of IRF-1 homodimers, Biochimie, vol.80, pp.659-664, 1998. ,
, Interplay between repressing and activating domains defines the transcriptional activity of IRF, 2000.
, Eur. J. Biochem, vol.267, pp.6753-6761
Comparative study on the immunogenicity between an HLA-A24-restricted cytotoxic T-cell epitope derived from survivin and that from its splice variant survivin-2B in oral cancer patients, J. Transl. Med, vol.7, p.1, 2009. ,
RelA-induced interferon response negatively regulates proliferation, PLoS One, 2015. ,
,
, Human CD25highFoxp3pos regulatory T cells differentiate into IL-17-producing cells, Blood, vol.112, pp.2340-2352
The macrophage IRF8/IRF1 regulome is required for protection against infections and is associated with chronic inflammation, J. Exp. Med, vol.213, pp.585-603, 2016. ,
Noncoding regions are the main source of targetable tumor-specific antigens, Sci. Transl. Med, vol.10, 2018. ,
Mechanisms and Regulation of Alternative Pre-mRNA Splicing, Annu. Rev. Biochem, 2015. ,
Alternative splicing variants of IRF-1 lacking exons 7, 8, and 9 in cervical cancer, Biochem. Biophys. Res. Commun, vol.347, pp.882-888, 2006. ,
Alternative splicing variants of IRF-1 lacking exons 7, 8, and 9 in cervical cancer, Biochem. Biophys. Res. Commun, vol.347, pp.882-888, 2006. ,
Revisiting the concept of targeting NFAT to control T cell immunity and autoimmune diseases, Front. Immunol, 2018. ,
Comparison of the Regulation of ?-Catenin Signaling by Type I, Type II and Type III Interferons in Hepatocellular Carcinoma Cells, PLoS One, 2012. ,
TGF-?1 Uses Distinct Mechanisms to Inhibit IFN-? Expression in CD4 + T Cells at Priming and at Recall: Differential Involvement of Stat4 and T-bet, J. Immunol, vol.174, pp.5950-5958, 2005. ,
TGF-?1 secreted by M2 phenotype macrophages enhances the stemness and migration of glioma cells via the SMAD2/3 signalling pathway, Int. J. Mol. Med, 2018. ,
, , 1997.
Regulation of alternative splicing by histone modifications, 2010. ,
T-bet is required for optimal production of IFN-gamma and antigen-specific T cell activation by dendritic cells, Proc. Natl. Acad. Sci. U. S. A, vol.100, pp.7749-7754, 2003. ,
,
The interleukin 12 p40 gene promoter is primed by interferon gamma in monocytic cells, J. Exp. Med, vol.183, pp.147-157, 1996. ,
Regulation of IL-10 and IL-12 production and function in macrophages and dendritic cells, 2015. ,
Absence of leucine zipper in the natural FOXP3Delta2Delta7 isoform does not affect dimerization but abrogates suppressive capacity, PLoS One, vol.4, p.6104, 2009. ,
IL-1? promotes Th17 differentiation by inducing alternative splicing of FOXP3, Sci. Rep, vol.5, 2015. ,
The role of DNA rearrangement and alternative RNA processing in the expression of immunoglobulin delta genes, Cell, vol.24, pp.353-365, 1981. ,
Regulatory T cells in the control of immune pathology, Nat. Immunol, vol.2, pp.816-822, 2001. ,
Cellular mechanisms of fatal earlyonset autoimmunity in mice with the T cell-specific targeting of transforming growth factor-beta receptor, Immunity, vol.25, pp.441-454, 2006. ,
Control of alternative splicing in immune responses: many regulators, many predictions, much still to learn, Immunol. Rev, vol.253, pp.216-236, 2013. ,
Alternative splicing networks regulated by signaling in human T cells, RNA, vol.18, pp.1029-1040, 2012. ,
IFN-gamma-mediated upmodulation of MHC class I expression activates tumor-specific immune response in a mouse model of prostate cancer, Vaccine, vol.28, pp.3548-3557, 2010. ,
A novel function of interferon regulatory factor-1: Inhibition of T h 2 cells by down-regulating the Il4 gene during Listeria infection, Int. Immunol, 2015. ,
A novel function of interferon regulatory factor-1: Inhibition of T h 2 cells by down-regulating the Il4 gene during Listeria infection, Int. Immunol, vol.27, pp.143-152, 2015. ,
A day in the life of the spliceosome, Nat. Rev. Mol. Cell Biol, vol.15, pp.108-121, 2014. ,
Signal-dependent regulation of splicing via phosphorylation of Sam68, Nature, vol.420, pp.691-695, 2002. ,
Challenging the dogma: the hidden layer of non-protein-coding RNAs in complex organisms, BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology, vol.25, issue.10, pp.930-939, 2003. ,
Natural recovery and protection from autoimmune encephalomyelitis: contribution of CD4+CD25+ regulatory cells within the central nervous system, J. Immunol, vol.175, pp.3025-3032, 2005. ,
Smad3 Is Essential for TGF-?1 to Suppress IL-2 Production and TCR-Induced Proliferation, but Not IL-2-Induced Proliferation, J. Immunol, vol.172, pp.4275-4284, 2004. ,
CD45 isoforms in T cell signalling and development, Immunol. Lett, vol.92, pp.125-134, 2004. ,
Alternative splicing of MALT1 controls signalling and activation of CD4 + T cells, Nat. Commun, vol.7, 2016. ,
Heterogeneous Nuclear Ribonucleoprotein K Is a Transcription Factor, 1996. ,
Molecular mechanisms by which T-bet regulates T-helper cell commitment, Immunol. Rev, 2010. ,
IL-4 enhances IL-10 production in Th1 cells: Implications for Th1 and Th2 regulation, 2017. ,
Regulated expression of a gene encoding a nuclear factor, IRF-1, that specifically binds to IFN-? gene regulatory elements, Cell, 1988. ,
Adenovirus E1A downregulates LMP2 transcription by interfering with the binding of Stat1 to IRF1, J. Biol. Chem, vol.275, pp.20406-20411, 2000. ,
Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins, J. Immunol, 1986. ,
Context-dependent regulatory mechanism of the splicing factor hnRNP L, Mol. Cell, vol.37, pp.223-234, 2010. ,
Alternative splicing factor/splicing factor 2 regulates the expression of the ? subunit of the human T cell receptor-associated CD3 complex, J. Biol. Chem, vol.285, pp.12490-12496, 2010. ,
The integrin ???8 mediates epithelial homeostasis through MT1-MMP-dependent activation of TGF-?1, J. Cell Biol, vol.157, pp.493-507, 2002. ,
, , 2010.
Robust enumeration of cell subsets from tissue expression profiles, Nat. Methods, vol.12, pp.453-457, 2015. ,
CD44 variant 6 is associated with prostate cancer metastasis and chemo-/radioresistance, Prostate, vol.74, pp.602-617, 2014. ,
Regulation of toll-like receptor signaling by the SF3a mRNA splicing complex, PLoS Genet, vol.11, p.1004932, 2015. ,
Cutting edge: Th1 cells facilitate the entry of Th17 cells to the central nervous system during experimental autoimmune encephalomyelitis, J. Immunol, vol.181, pp.3750-3754, 2008. ,
Mechanisms underlying lineage commitment and plasticity of helper CD4 + T cells, Science, vol.327, pp.1098-1102, 2010. ,
Regulation of CD45 alternative splicing by heterogeneous ribonucleoprotein, hnRNPLL. Science (80-. ), vol.321, pp.686-691, 2008. ,
T-bet employs diverse regulatory mechanisms to repress transcription, Trends Immunol, 2012. ,
Requirement for IRF-1 in the microenvironment supporting development of natural killer cells, Nature, vol.391, pp.700-703, 1998. ,
CD4+ T lymphocytes: a critical component of antitumor immunity, Cancer Invest, vol.23, pp.413-419, 2005. ,
Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing, Nat. Genet, vol.40, pp.1413-1415, 2008. ,
Genome-wide Analysis Reveals SR Protein Cooperation and Competition in Regulated Splicing, Mol. Cell, 2013. ,
Pre-mRNA splicing during transcription in the mammalian system, Wiley Interdiscip. Rev. RNA, 2011. ,
Exacerbations of multiple sclerosis in patients treated with gamma interferon, Lancet, vol.1, pp.893-895, 1987. ,
Role of TGF? in regulation of the tumor microenvironment and drug delivery (review), Int. J. Oncol, vol.46, pp.933-943, 2015. ,
The interferon regulatory transcription factor IRF-1 controls positive and negative selection of CD8+ thymocytes, Immunity, vol.7, pp.243-254, 1997. ,
The cholesterol biosynthesis pathway regulates IL-10 expression in human Th1 cells, Nat. Commun, 2019. ,
TGF-?, bone morphogenetic protein, and activin signaling and the tumor microenvironment, Cold Spring Harb. Perspect. Biol, vol.9, 2017. ,
Regulation of alternative splicing of CD44 in cancer, Cell. Signal, vol.26, pp.2234-2239, 2014. ,
A crucial role for CD44 in inflammation, Trends Mol. Med, vol.7, pp.213-221, 2001. ,
mRNA capping: Biological functions and applications, Nucleic Acids Res, 2016. ,
Cancer immunotherapy using checkpoint blockade. Science (80-. ), vol.359, pp.1350-1355, 2018. ,
Transcription termination by nuclear RNA polymerases, Genes Dev, 2009. ,
Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer, vol.348, pp.124-128, 2015. ,
Functional Demarcation of Active and Silent Chromatin Domains in Human HOX Loci by Noncoding RNAs, Cell, vol.129, issue.7, pp.1311-1323, 2007. ,
CD8 T cell memory, Semin. Immunol, 2004. ,
URL : https://hal.archives-ouvertes.fr/pasteur-00488854
Regulation of NF-kappaBdependent lymphocyte activation and development by paracaspase, Science, vol.302, pp.1581-1584, 2003. ,
A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language?, Cell, vol.146, issue.3, pp.353-358, 2011. ,
Tumor mutational load predicts survival after immunotherapy across multiple cancer types, Nat. Genet, vol.51, pp.202-206, 2019. ,
Regulation of the immune response by TGF-?: From conception to autoimmunity and infection, Cold Spring Harb. Perspect. Biol, vol.9, 2017. ,
Regulation of the expression of distinct human secreted IgE proteins produced by alternative RNA splicing, Biochemical Society Transactions, pp.383-387, 1997. ,
Splicing in immune cells-mechanistic insights and emerging topics, Int. Immunol, vol.29, pp.173-181, 2017. ,
Interferon-?-induced activation of Signal Transducer and Activator of Transcription 1 (STAT1) up-regulates the tumor suppressing microRNA-29 family in melanoma cells, Cell Commun. Signal, 2012. ,
A MAGE-A3 peptide presented by HLA-DP4 is recognized on tumor cells by CD4+ cytolytic T lymphocytes, Cancer Res, vol.60, pp.6272-6275, 2000. ,
RNA mis-splicing in disease, Nat. Rev. Genet, vol.17, pp.19-32, 2016. ,
Epitope landscape in breast and colorectal cancer, Cancer Res, vol.68, pp.889-892, 2008. ,
Heterogeneous nuclear ribonucleoprotein (hnRNP) L promotes DNA damageinduced cell apoptosis by enhancing the translation of p53, Oncotarget, 2017. ,
Single-cell transcriptomics reveals bimodality in expression and splicing in immune cells, Nature, vol.498, pp.236-240, 2013. ,
An emt-driven alternative splicing program occurs in human breast cancer and modulates cellular phenotype, PLoS Genet, vol.7, 2011. ,
Mechanistic insights into precursor messenger RNA splicing by the spliceosome, Nat. Rev. Mol. Cell Biol, vol.18, pp.655-670, 2017. ,
Mutant U2AF1 Expression Alters Hematopoiesis and Pre-mRNA Splicing In Vivo, Cancer Cell, vol.27, pp.631-643, 2015. ,
Rbfox-Splicing Factors Maintain Skeletal Muscle Mass by Regulating Calpain3 and Proteostasis, Cell Rep, 2018. ,
Identification of multiple HLA-DR-restricted epitopes of the tumor-associated antigen CAMEL by CD4+ Th1/Th2 lymphocytes, J. Immunol, vol.172, pp.5095-5102, 2004. ,
Transcriptional and functional consequences of TP53 splice mutations in colorectal cancer, 2019. ,
Convergence of acquired mutations and alternative splicing of CD19 enables resistance to CART-19 immunotherapy, Cancer Discov, vol.5, pp.1282-1295, 2015. ,
Chimeric antigen receptor T cells shape myeloid cell function within the tumor microenvironment through IFN-? and GM-CSF, J. Immunol, vol.188, pp.6389-6398, 2012. ,
Computational and analytical challenges in single-cell transcriptomics, Nat. Rev. Genet, vol.16, pp.133-145, 2015. ,
A global view of gene activity and alternative splicing by deep sequencing of the human transcriptome, Science, vol.321, pp.956-960, 2008. ,
CD4+ T cells are required for the maintenance, not programming, of memory CD8+ T cells after acute infection, Nat. Immunol, vol.5, pp.927-933, 2004. ,
Aberrant RNA splicing in cancer; expression changes and driver mutations of splicing factor genes, Oncogene, vol.35, pp.2413-2427, 2016. ,
Tob is a negative regulator of activation that is expressed in anergic and quiescent T cells, Nat. Immunol, vol.2, pp.1174-1182, 2001. ,
Low expression of interferon regulatory factor-1 and identification of novel exons skipping in patients with chronic myeloid leukaemia, Br. J. Haematol, vol.119, pp.46-53, 2002. ,
Th17 plasticity and its relevance to inflammatory bowel disease, J. Autoimmun, vol.87, pp.38-49, 2018. ,
, , 2002.
, Abrogation of IRF-1 response by high-risk HPV E7 protein in vivo, Cancer Lett, vol.179, pp.205-212
IRF1: A deus ex machina in TH1 differentiation, Nat. Immunol, 2008. ,
The transcription factor IRF1 dictates the IL-21-dependent anticancer functions of T H9 cells, Nat. Immunol, vol.15, pp.758-766, 2014. ,
M2-polarised macrophages in infantile haemangiomas: correlation with promoted angiogenesis, J. Clin. Pathol, vol.66, pp.1058-1064, 2013. ,
Deficiency of interferongamma or its receptor promotes colorectal cancer development, J. Interferon Cytokine Res, vol.35, pp.273-280, 2015. ,
, Global Mapping of H3K4me3 and H3K27me3 Reveals Specificity and Plasticity in Lineage Fate Determination of Differentiating CD4+ T Cells. Immunity, 2009.
Expression of CD44 Variant Proteins in Human Colorectal Cancer Is Related to Tumor Progression, Cancer Res, vol.53, pp.4754-4756, 1993. ,
Tumor-specific CD4+ T cells render the tumor environment permissive for infiltration by low-avidity CD8+ T cells, J. Immunol, vol.180, pp.3122-3131, 2008. ,
Transforming growth factor-? in stem cells and tissue homeostasis, Bone Res, vol.6, 2018. ,
, The Transcription Factor GATA3 Actively Represses RUNX3 Protein-Regulated Production of Interferon-?. Immunity, 2010.
TRAF6 mediates Smad-independent activation of JNK and p38 by TGF-beta, Mol. Cell, vol.31, pp.918-924, 2008. ,
TRAF6 mediates Smad-independent activation of JNK and p38 by TGF-beta, Mol. Cell, vol.31, pp.918-924, 2008. ,
Regulation of TGF-beta signaling by Smad7, Acta Biochim. Biophys. Sin. (Shanghai), vol.41, pp.263-272, 2009. ,
The IRF family of transcription factors inception, impact and implications in oncogenesis, 2012. ,
Functional impact of splice isoform diversity in individual cells, Biochem. Soc. Trans, vol.44, pp.1079-1085, 2016. ,
The U2AF1S34F mutation induces lineage-specific splicing alterations in myelodysplastic syndromes, J. Clin. Invest, vol.127, pp.2206-2221, 2017. ,
hnRNP-U enhances the expression of specific genes by stabilizing mRNA, FEBS Lett, 2007. ,
,
Deep-learning augmented RNA-seq analysis of transcript splicing, Nat. Methods, vol.16, pp.307-310, 2019. ,
, CD44 promotes Kras-dependent lung adenocarcinoma, vol.32, pp.5186-5190, 2013.
, Plasticity of CD4+ T Cell Lineage Differentiation. Immunity, 2009.
Overexpression of HnRNP A1 promotes tumor invasion through regulating CD44v6 and indicates poor prognosis for hepatocellular carcinoma, Int. J. Cancer, vol.132, pp.1080-1089, 2013. ,
, , 2005.
, HIV-1-specific IFN-gamma/IL-2-secreting CD8 T cells support CD4-independent proliferation of HIV-1-specific CD8 T cells, Proc. Natl. Acad. Sci. U. S. A, vol.102, pp.7239-7244
RNA splicing control: yet another gene regulatory role for long nuclear noncoding RNAs, RNA Biology, vol.8, issue.6, pp.968-977 ,
, PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: Mechanisms, response biomarkers, and combinations. Sci. Transl, 2016.
, Figure S1C) and Caspase-9 (Figure S1D) cleavage in Casp3 +/+ cells with no differences observed neither in Caspase-7 (Figure S1E
, After 24 hours of treatment, the medium containing docetaxel was removed; observed that apoptosis and particularly Caspase-3 dependent apoptosis correlated with increased neo-vessel formation and vasculature stabilization, apoptosis (Figure S1G), nor in cell growth (Figure S1H) between both cell lines
, Our results could be in accordance with different studies. Indeed, PKC? was shown to induce stabilization of VEGFA translation without impacting its transcription (42). Moreover, AKT was
, As once cleaved, Caspase-3 translocates into the nucleus, we wondered whether the induction of proangiogenic genes could be due to an unexpected transcriptional function of cleaved
This interaction needs the 15-amino acid motif "AYSTAPGYYSWRNSK" and the formation of the tertiary structure between small and large subunits of Caspase-3. Nevertheless, the proteolytic activity of Caspase-3 is not necessary for its transcriptional activity, p.163 ,
Nuclear translocation of caspase-3 is dependent on its proteolytic activation and recognition of a substrate-like protein(s), The Journal of biological chemistry, vol.280, issue.2, 2005. ,
Caspase 3-mediated stimulation of tumor cell repopulation during cancer radiotherapy, Nature medicine, vol.17, issue.7, pp.860-866, 2011. ,
Dying tumor cells stimulate proliferation of living tumor cells via caspase-dependent protein kinase Cdelta activation in pancreatic ductal adenocarcinoma, Molecular oncology, vol.9, issue.1, pp.105-119, 2015. ,
Caspase 3 promotes surviving melanoma tumor cell growth after cytotoxic therapy, The Journal of investigative dermatology, vol.134, issue.6, 2014. ,
Caspase 3 in dying tumor cells mediates post-irradiation angiogenesis, Oncotarget, vol.6, issue.32, pp.32353-67, 2015. ,
A Dual Role of Caspase-8 in Triggering and Sensing Proliferation-Associated DNA Damage, a Key Determinant of Liver Cancer Development, Cancer Cell, vol.32, issue.3, pp.342-59, 2017. ,
More alive than dead: non-apoptotic roles for caspases in neuronal development, plasticity and disease, Cell death and differentiation, vol.24, issue.8, pp.1411-1432, 2017. ,
Caspases maintain tissue integrity by an apoptosis-independent inhibition of cell migration and invasion, Nat Commun, vol.9, issue.1, 2018. ,
Caspase-3 Regulates YAP-Dependent Cell Proliferation and Organ Size, Mol Cell, vol.70, issue.4, pp.573-87, 2018. ,
The transcription factor IRF1 dictates the IL-21-dependent anticancer functions of TH9 cells, Nature immunology, vol.15, issue.8, pp.758-66, 2014. ,
The receptor NLRP3 is a transcriptional regulator of TH2 differentiation, Nature immunology, vol.16, issue.8, 2015. ,
Survivin-3B potentiates immune escape in cancer but also inhibits the toxicity of cancer chemotherapy, Cancer research, vol.73, issue.17, pp.5391-401, 2013. ,
Melanoma mouse model implicates metabotropic glutamate signaling in melanocytic neoplasia, Nature genetics, vol.34, issue.1, 2003. ,
Early predictive value of non-response to docetaxel in neoadjuvant chemotherapy in breast cancer using 18F-FDG-PET, Anticancer Res, vol.34, issue.1, pp.221-227, 2014. ,
Use of [(18)F]-FDG PET to predict response to neoadjuvant trastuzumab and docetaxel in patients with HER2-positive breast cancer, and addition of bevacizumab to neoadjuvant trastuzumab and docetaxel in [(18)F]-FDG PETpredicted non-responders (AVATAXHER): an open-label, randomised phase 2 trial, Lancet Oncol, vol.15, issue.13, pp.70475-70484, 2014. ,
Correlation of angiogenesis with 18F-FMT and 18F-FDG uptake in non-small cell lung cancer, Cancer science, vol.100, issue.4, pp.753-761, 2009. ,
Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool, BMC Bioinformatics, 2013. ,
Enrichr: a comprehensive gene set enrichment analysis web server 2016 update, Nucleic acids research, vol.44, issue.W1, 2016. ,
Adrenergic signaling promotes angiogenesis through endothelial cell-tumor cell crosstalk, Endocr Relat Cancer, vol.21, issue.5, 2014. ,
Oxytocin stimulates migration and invasion in human endothelial cells, Br J Pharmacol, vol.153, issue.4, pp.728-764, 2008. ,
Oxytocin stimulates in vitro angiogenesis via a Pyk-2/Src-dependent mechanism, Experimental cell research, vol.315, issue.18, pp.3210-3219, 2009. ,
Regulation of angiogenic behaviors by oxytocin receptor through Gli1-indcued transcription of HIF-1alpha in human umbilical vein endothelial cells, Biomed Pharmacother, vol.90, pp.928-962, 2017. ,
Thyrotropin (TSH)-induced production of vascular endothelial growth factor in thyroid cancer cells in vitro: evaluation of TSH signal transduction and of angiogenesis-stimulating growth factors, J Clin Endocrinol Metab, vol.89, issue.12, pp.6139-6184, 2004. ,
Muscarinic receptors participation in angiogenic response induced by macrophages from mammary adenocarcinoma-bearing mice, Breast Cancer Res, vol.7, issue.3, 2005. ,
Pro-inflammatory angiogenesis is mediated by p38 MAP kinase, J Cell Physiol, vol.226, issue.3, pp.800-808, 2011. ,
5-hydroxytryptamine and its receptors in systemic vascular walls, Biol Pharm Bull, vol.36, issue.9, pp.1416-1425, 2013. ,
Platelet-Derived Growth Factor (PDGF)/PDGF Receptors (PDGFR) Axis as Target for Antitumor and Antiangiogenic Therapy, Pharmaceuticals (Basel), vol.3, issue.3, pp.572-99, 2010. ,
Inhibition of NF-kappaB activity decreases the VEGF mRNA expression in MDA-MB-231 breast cancer cells, Breast cancer research and treatment, vol.73, issue.3, pp.237-280, 2002. ,
The Caspase ,
Clinical cancer research : an official journal of the American Association for, Cancer Research, vol.25, issue.12, pp.3732-3775, 2019. ,
The role of individual caspases in cell death induction by taxanes in breast cancer cells, Cancer cell international, vol.15, issue.1, 2015. ,
Nuclear entry of active caspase-3 is facilitated by its p3-recognition-based specific cleavage activity, Cell research, vol.20, issue.2, pp.211-233, 2010. ,
Catalytic activity of caspase-3 is required for its degradation: stabilization of the active complex by synthetic inhibitors, Cell death and differentiation, vol.11, issue.4, pp.439-486, 2004. ,
BindN: a web-based tool for efficient prediction of DNA and RNA binding sites in amino acid sequences, Nucleic acids research, vol.34, 2006. ,
Hallmarks of cancer: the next generation, Cell, vol.144, issue.5, 2011. ,
Caspase-dependent non-apoptotic processes in development, Cell death and differentiation, vol.24, issue.8, 2017. ,
A Novel Non-Apoptotic Role of Procaspase-3 in the Regulation of Mitochondrial Biogenesis Activators, J Cell Biochem, vol.119, issue.1, pp.347-57, 2018. ,
Exiting the dark side: A vital role for Caspase-3 in Yap signaling, Mol Cell Oncol, vol.5, issue.4, 2018. ,
Dying glioma cells establish a proangiogenic microenvironment through a caspase 3 dependent mechanism, Cancer letters, vol.385, 2017. ,
Lipid-induced toxicity stimulates hepatocytes to release angiogenic microparticles that require Vanin-1 for uptake by endothelial cells, Science signaling, vol.6, issue.296, 2013. ,
Caspase-3-mediated cleavage of the NFkappa B subunit p65 at the NH2 terminus potentiates naphthoquinone analoginduced apoptosis, The Journal of biological chemistry, vol.276, issue.27, 2001. ,
Caspase-8 contributes to angiogenesis and chemotherapy resistance in glioblastoma, Elife, 2017. ,
Jahani-Asl A, Basak A, Tsang BK. Caspase-3-mediated cleavage of Akt: involvement of non-consensus sites and influence of phosphorylation, Cell Signal, vol.20, issue.5, pp.969-77, 2007. ,
Caspase-3-dependent cleavage of Akt modulates tau phosphorylation via GSK3beta kinase: implications for Alzheimer's disease, Mol Psychiatry, vol.22, issue.7, 2017. ,
The mechanisms on apoptosis by inhibiting VEGF expression in human breast cancer cells, International immunopharmacology, vol.9, issue.4, pp.389-95, 2009. ,
Vascular endothelial growth factor promotes fibrosis resolution and repair in mice, Gastroenterology, vol.146, issue.5, 2014. ,
Caspase-3-mediated secretion of connective tissue growth factor by apoptotic endothelial cells promotes fibrosis, Cell death and differentiation, vol.17, issue.2, 2010. ,
Tumor microenvironment and progression of pancreatic cancer, Experimental oncology, vol.32, issue.3, pp.128-159, 2010. ,
Expression of Vascular Endothelial Growth Factor in Ovarian Cancer Inhibits Tumor Immunity through the Accumulation of Myeloid-Derived Suppressor Cells. Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. ,
Identification of NRF2, a member of the NF-E2 family of transcription factors, as a substrate for caspase-3(-like) proteases, Cell death and differentiation, vol.6, issue.9, 1999. ,
Feasibility study for clinical application of caspase-3 inhibitors in Pemphigus vulgaris, Exp Dermatol, vol.26, issue.12, 2017. ,
Randomised clinical trial: emricasan versus placebo significantly decreases ALT and caspase 3/7 activation in subjects with non-alcoholic fatty liver disease ,
, Aliment Pharmacol Ther, vol.49, issue.1, 2019.
Apoptosis at a distance: remote activation of caspase-3 occurs early after myocardial infarction, Molecular and cellular biochemistry, vol.281, issue.1-2, pp.45-54, 2006. ,
Danshen improves damaged cardiac angiogenesis and cardiac function induced by myocardial infarction by modulating HIF1alpha/VEGFA signaling pathway, International journal of clinical and experimental medicine, vol.8, issue.10, pp.18311-18319, 2015. ,
Puerarin accelerate scardiac angiogenesis and improves cardiac function of myocardial infarction by upregulating VEGFA, Ang-1 and Ang-2 in rats, International journal of clinical and experimental medicine, vol.8, issue.11, pp.20821-20829, 2015. ,
Caspase 3 activation is essential for neuroprotection in preconditioning, Proceedings of the National Academy of Sciences of the United States of America, vol.100, issue.2, 2003. ,
Role of vascular endothelial growth factor in neuronal DNA damage and repair in rat brain following a transient cerebral ischemia, Journal of neuroscience research, vol.70, issue.2, 2002. ,
VEGF at the neurovascular interface: therapeutic implications for motor neuron disease, Biochimica et biophysica acta, vol.1762, issue.11-12, 2006. ,
VEGF signalling controls GnRH neuron survival via NRP1 independently of KDR and blood vessels, Development, vol.138, issue.17, 2011. ,
Role of VEGF and VEGFR2 Receptor in Reversal of ALS-CSF Induced Degeneration of NSC-34 Motor Neuron Cell Line, Molecular neurobiology, vol.51, issue.3, pp.995-1007, 2015. ,
, Caspase-3-subcutaneous injection of CT-26 cells followed by IP injection of FU (50mg/kg) and irinotecan (40mg/kg) with weekly IP injection of Z-FA-FMK control inhibitor or of Z-DEVD-FMK Caspase-3 RT-PCR analysis of VEGFA expression. Data are presented as mean ± SD. Figure 5: Cleaved Caspase-3 could down-regulate anti-apoptotic genes. A. RNA sequencing analysis of MCF-7 Caspase-3 +/+ downregulated genes with Enrichr NCI-Nature pathway database, (50mg/kg) (FU) and irinotecan (40mg/kg) with or without injections of
RNA sequencing analysis of the 36 genes in common in B with Enrichr NCI-Nature pathway database. D. Fold change of enriched genes in A showing RNA sequencing data of Caspase-3 +/+ and -/-MCF-7 cells. E. Venn diagram of A enriched genes in Caspase-3 +/+ MCF-7 cells and Caspase-3 interacted genes. F. RNA sequencing analysis Caspase-3 non-interacted genes in MCF-7 Caspase-3 +/+ cells with Enrichr ENCODE and ChEA Consensus TFs from ChIP ,
, Rev: TTCTTTGCAGCTCCTTCGTT), human ?-actin an emission scan to evaluate tumor metabolism after 18F-FDG uptake (30min static acquisition, tumor-centered, ATGGAGGGGAATACAGCCC
, Cell culture supernatants were assayed by ELISA for human VEGFA (Invitrogen), according to the manufacturer's protocol
, Western blot analyses were conducted as described previously [2] with the following primary antibodies: Cleaved Caspase-3, Cleaved Caspase-7, Cleaved Caspase-8, Cleaved Caspase-9, Procaspase-3, Procaspase-6, Procaspase-7
, Caspase-3 -/-MCF-7 cells were transiently transfected with procaspase-3-GFP plasmid for 48 h. Then, cells were treated or not with docetaxel, Fluorescence microscopy
, For transfection experiments, cells were transfected with 2 different siRNA specific for human NF-?B (GGATCCTTCTTTGACTCAT and CCACCTTCATTCTCAACTT), PKC (GCAAGAAGAACAATGGCAA and GCATGAATGTGCACCATAA), Pro-caspase-3 (GGGAAACATTCAGAAACTT and GCACCTGGTTATTATTCTT), Pro-caspase-6 (GCAGATAGAGACAATCTTA and GCGAAGGCAATCACATTTA)
Identification of cyclooxygenase-2 as a major actor of the transcriptomic adaptation of endothelial and tumor cells to cyclic hypoxia: effect on angiogenesis and metastases, Clin Cancer Res, vol.16, issue.2, pp.410-419, 2010. ,
Association of p53 gene alterations with the expression of antiapoptotic survivin splice variants in breast cancer, Oncogene, vol.26, issue.2, pp.290-297, 2007. ,
Overexpression of caspase-3s splice variant in locally advanced breast carcinoma is associated with poor response to neoadjuvant chemotherapy, Clin Cancer Res, vol.12, pp.5794-800, 2006. ,
Biochemical characteristics of caspases-3 ,
, J Biol Chem, vol.272, issue.41, pp.25719-25742, 1997.
Lactate influx through the endothelial cell monocarboxylate transporter MCT1 supports an NF-kappaB/IL-8 pathway that drives tumor angiogenesis, Cancer Res, vol.71, issue.7, pp.2550-60, 2011. ,
BindN: a web-based tool for efficient prediction of DNA and RNA binding sites in amino acid sequences, Nucleic Acids Res, vol.34, pp.243-251, 2006. ,
Distinct expression of Survivin splice variants in breast carcinomas, Int J Oncol, 2005. ,
, Caspase-3. Firefly luciferase assay with various combinations of Caspase-3 small subunit plasmid, siRNA against Caspase-3, -6 or -7 transfection and docetaxel (10 nM) treatment during 24h
Pharmacological inhibition of Caspase-3 blocks VEGFA induction in mouse cells. RT-PCR analysis of VEGFA expression in 4T1 and CT-26 cells treated or not with docetaxel (10 nM) and with Z-FA-FMK control inhibitor or with Z-DEVD-FMK Caspase-3 inhibitor. B. Targeting Caspase-6 and ,
, Tumor growth in BALB/c mice after subcutaneous injection of CT-26 cells followed by intraperitoneal (IP) injections of 5-fluorouracile (FU) (50 mg/kg) and irinotecan (40mg/kg) with or without weekly injections of Caspase-6 or -7-specific siRNA into the tumor
, Il est maintenant clairement établi que le système immunitaire peut influencer la réponse du cancer au traitement. Cependant, l'influence du microenvironnement tumoral sur les cellules immunitaires n'est pas complètement comprise
nous avons montré que le microenvironnement tumoral, en augmentant les événements d'épissage alternatif, induisait l'expression d'une isoforme alternative du facteur de transcription IRF1 dans les cellules Th1. En outre, nous avons également montré, chez la souris comme chez l'homme, que l'isoforme alternative d'IRF1 altère l'activité transcriptionnelle d'IRF1 sur le promoteur de Il12rb1, entraînant une diminution de la sécrétion ,
, Ainsi, l'expression de l'isoforme courte d'IRF1 augmente au sein du microenvironnement tumoral, et bloquer son apparition pourrait potentialiser l'effet anti-tumoral des cellules Th1