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Fibroblast Heterogeneity and Immunosuppressive Environment in Human Breast Cancer

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

Edité par CCSD ; Elsevier -

Comment inBreast cancer: Fibroblast subtypes alter the microenvironment. [Nat Rev Clin Oncol. 2018]. International audience. 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.

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