| Literature DB >> 29455927 |
Ana Costa1, Yann Kieffer1, Alix Scholer-Dahirel2, Floriane Pelon1, Brigitte Bourachot1, Melissa Cardon1, Philemon Sirven2, Ilaria Magagna1, Laetitia Fuhrmann3, Charles Bernard1, Claire Bonneau1, Maria Kondratova4, Inna Kuperstein4, Andrei Zinovyev4, Anne-Marie Givel1, Maria-Carla Parrini5, Vassili Soumelis6, Anne Vincent-Salomon3, Fatima Mechta-Grigoriou7.
Abstract
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.Entities:
Keywords: CAF; FOXP3; T lymphocytes; Treg; breast cancers; fibroblasts; heterogeneity; regulatory T cell; stroma; triple-negative
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Year: 2018 PMID： 29455927 DOI： 10.1016/j.ccell.2018.01.011
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743