FOXP3型
免疫抑制
癌症研究
肿瘤微环境
三阴性乳腺癌
乳腺癌
生物
白细胞介素2受体
效应器
免疫学
T细胞
免疫系统
化学
癌症
遗传学
作者
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,Andrei Zinovyev,Anne-Marie Givel,Maria Carla Parrini,Vassili Soumelis,Anne Vincent‐Salomon,Fatima Mechta‐Grigoriou
出处
期刊:Cancer Cell
[Elsevier]
日期:2018-03-01
卷期号:33 (3): 463-479.e10
被引量:1061
标识
DOI:10.1016/j.ccell.2018.01.011
摘要
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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