Fibroblast Heterogeneity and Immunosuppressive Environment in Human Breast Cancer

被引：1436

作者：

Costa, Ana ^{[1
,2
]}

Kieffer, Yann ^{[1
,2
]}

Scholer-Dahirel, Alix ^{[1
,2
,3
]}

Pelon, Floriane ^{[1
,2
]}

Bourachot, Brigitte ^{[1
,2
]}

Cardon, Melissa ^{[1
,2
]}

Sirven, Philemon ^{[1
,2
,3
]}

Magagna, Ilaria ^{[1
,2
]}

Fuhrmann, Laetitia ^{[5
]}

Bernard, Charles ^{[1
,2
]}

Bonneau, Claire ^{[1
,2
]}

Kondratova, Maria ^{[6
]}

Kuperstein, Inna ^{[6
]}

Zinovyev, Andrei ^{[6
]}

Givel, Anne-Marie ^{[1
,2
]}

Parrini, Maria-Carla ^{[4
]}

Soumelis, Vassili ^{[3
]}

Vincent-Salomon, Anne ^{[5
]}

Mechta-Grigoriou, Fatima ^{[1
,2
]}

机构：

[1] PSL Res Univ, Inst Curie, Equipe Labelisee Ligue Natl Canc, Stress & Canc Lab, 26 Rue Ulm, F-75005 Paris, France

[2] INSERM, U830, F-75005 Paris, France

[3] PSL Res Univ, INSERM, Integrat Biol Human Dendrit Cells & T Cells Lab, Inst Curie,U932, 26 Rue Ulm, F-75005 Paris, France

[4] PSL Res Univ, INSERM, Anal Transduct Pathway, Inst Curie,U830, 26 Rue Ulm, F-75005 Paris, France

[5] Hosp Grp, Dept Pathol, Inst Curie, 26 Rue Ulm, F-75248 Paris, France

[6] PSL Res Univ, Mines Paris Tech, INSERM, Inst Curie,U900, F-75005 Paris, France

来源：

CANCER CELL | 2018年 / 33卷 / 03期

关键词：

CARCINOMA-ASSOCIATED FIBROBLASTS; REGULATORY T-CELLS; TUMOR MICROENVIRONMENT; ACTIVATION PROTEIN; PROGNOSTIC-SIGNIFICANCE; ANTITUMOR IMMUNITY; PANCREATIC-CANCER; STROMAL CELLS; EXPRESSION; METASTASIS;

D O I：

10.1016/j.ccell.2018.01.011

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

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 CD25(High)FOXP3(High), 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.

引用

页码：463 / +

页数：27

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