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Fibroblast Heterogeneity and Immunosuppressive Environment in Human Breast Cancer

2018; Cell Press; Volume: 33; Issue: 3 Linguagem: Inglês

10.1016/j.ccell.2018.01.011

1878-3686

Ana Costa, Yann Kieffer, Alix Scholer‐Dahirel, Floriane Pelon, Brigitte Bourachot, Mélissa Cardon, Philémon Sirven, Ilaria Magagna, Laetitia Fuhrmann, Charles Bernard, Claire Bonneau, Maria Kondratova, Inna Kuperstein, Andreï Zinovyev, Anne-Marie Givel, Maria‐Carla Parrini, Vassili Soumelis, Anne Vincent‐Salomon, Fatima Mechta‐Grigoriou,

Immune cells in cancer

Carcinoma-associated fibroblasts (CAF) are key players in the tumor microenvironment. Here, we characterize four CAF subsets in breast cancer with distinct properties and levels of activation. Two myofibroblastic subsets (CAF-S1, CAF-S4) accumulate differentially in triple-negative breast cancers (TNBC). CAF-S1 fibroblasts promote an immunosuppressive environment through a multi-step mechanism. By secreting CXCL12, CAF-S1 attracts CD4+CD25+ T lymphocytes and retains them by OX40L, PD-L2, and JAM2. Moreover, CAF-S1 increases T lymphocyte survival and promotes their differentiation into CD25HighFOXP3High, through B7H3, CD73, and DPP4. Finally, in contrast to CAF-S4, CAF-S1 enhances the regulatory T cell capacity to inhibit T effector proliferation. These data are consistent with FOXP3+ T lymphocyte accumulation in CAF-S1-enriched TNBC and show how a CAF subset contributes to immunosuppression.