Skip to Main content Skip to Navigation
Theses

Les lymphocytes T CD4 régulateurs dans le cancer du sein, recrutement, enrichissement par les cellules dendritiques plasmacytoïdes et impact de l’axe de co-stimulation ICOS/ICOSL

Abstract : Tumor immunosbversion favors disease progression and is mediated by increased IL-10 secretion, reduced type-I IFN production and regulatory T cell (Treg) accumulation among CD4+ T cell in breast tumor. We showed that the presence of high number of both Treg and/or plasmacytoid DC (pDC) a subpopulation of antigen presenting celles correlates with poor prognosis in breast carcinoma. We previoously demonstrated that CCR4+ Treg are recruited from the periphery trough CCL22 production by breast tumor cells. Tumor-asssociated Treg (Ta-Treg) are highly activated (GITRhighHDLA-DRhighCD39high), show a selective expression of high levels of ICOS and proliferate in situ (Ki-67+). Tumor associated (Ta-) pDC express a partially activated phenotype but their type-1 interferon (IFN) production is strongly impaired in human tumors. pDc secretion of type-I IFN is linked to their capacity to induce anti-viral and anti-tumor immunity in mice models. We shown that 1) Ta-Treg and Ta-pDC colocalize in breast tumor section and 2) TapDC favor Ta-Treg proliferation and IL-10 secretion by CD4+ T cells in absence of type-I IFN. Ogf importance, targeting ICOS with a neutralizing antibody suppresses Ta-Treg proliferation as well as IL-10 secretion inpDC/CD4+ T cell co-culture, demonstrationg a riole of ICOS-ICOS-L interaction in Ta-Treg proliferation mediated by Ta-pDC. At the end, we report that high ICOS expression in breast tumor sections is associated with reduced patient's overall and disease free survival. Altogether these observations suggest that ICOS in breat cancer may represent a therapeutic target to restore anti-tumor immunity
Document type :
Theses
Complete list of metadata

https://tel.archives-ouvertes.fr/tel-00981636
Contributor : ABES STAR :  Contact
Submitted on : Tuesday, April 22, 2014 - 3:38:11 PM
Last modification on : Tuesday, October 19, 2021 - 11:07:41 PM
Long-term archiving on: : Monday, April 10, 2017 - 4:36:29 PM

File

TH2012_Faget_julien.pdf
Version validated by the jury (STAR)

Identifiers

  • HAL Id : tel-00981636, version 1

Collections

Citation

Julien Faget. Les lymphocytes T CD4 régulateurs dans le cancer du sein, recrutement, enrichissement par les cellules dendritiques plasmacytoïdes et impact de l’axe de co-stimulation ICOS/ICOSL. Médecine humaine et pathologie. Université Claude Bernard - Lyon I, 2012. Français. ⟨NNT : 2012LYO10310⟩. ⟨tel-00981636⟩

Share

Metrics

Record views

556

Files downloads

4008