Tumor associated regulatory CD4+ T cell in breast cancer, recruitment, and role of ICOS/ICOS-L interaction in their activation by altered plasmacytoïde dendritic cells
type: Dataset
description: 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
identifier: NNT: 2012LYO10310
issued: 2026-05-05T13:48:20.954613
language: fr
modified: 2026-05-05T13:48:20.954618
contact point: Organization
  fn: CCSD
keyword: breast-cancer
keyword: cancer-du-sein
keyword: cd4-t-cell
keyword: cellules-dendritiques
keyword: dendritics-cells
keyword: immunologie
keyword: immunology
keyword: immunotherapie
keyword: immunotherapy
keyword: infoeu-reposemanticsdoctoralthesis
keyword: lymphocytes-t-cd4
keyword: sdvmheplife-sciences-q-biohuman-health-and-pathology
keyword: theses
landing page: https://theses.hal.science/tel-00981636

Tumor associated regulatory CD4+ T cell in breast cancer, recruitment, and role of ICOS/ICOS-L interaction in their activation by altered plasmacytoïde dendritic cells
type: Distribution
format: HTML
issued: 2026-05-05T13:48:20.958121
modified: 2026-05-05T13:48:20.940987
access URL: https://theses.hal.science/tel-00981636

test_moissonnage_selune
type: Agent