期刊
NATURE COMMUNICATIONS
卷 11, 期 1, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-020-17046-2
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资金
- Institut National de la Sante et de la Recherche Medicale (INSERM)
- Association pour la Recherche sur le Cancer (ARC)
- Institut Curie
- Agence Nationale pour la Recherche (ANR Emergence program)
- Labex DCBIOL [ANR-10-IDEX-0001-02 PSL*, ANR-11-LABX0043]
- SIRIC [INCa-DGOS-Inserm_12554, INCa-DGOS-Inserm_4654]
- Ligue Nationale Contre le Cancer
- University Research Priority Program (URPP)
- Institut National du Cancer (INCa)
- IGR-Curie Clinical Investigation Center [1428]
Tumor-draining lymph node (TDLN) invasion by metastatic cells in breast cancer correlates with poor prognosis and is associated with local immunosuppression, which can be partly mediated by regulatory T cells (Tregs). Here, we study Tregs from matched tumor-invaded and non-invaded TDLNs, and breast tumors. We observe that Treg frequencies increase with nodal invasion, and that Tregs express higher levels of co-inhibitory/stimulatory receptors than effector cells. Also, while Tregs show conserved suppressive function in TDLN and tumor, conventional T cells (Tconvs) in TDLNs proliferate and produce Th1-inflammatory cytokines, but are dysfunctional in the tumor. We describe a common transcriptomic signature shared by Tregs from tumors and nodes, including CD80, which is significantly associated with poor patient survival. TCR RNA-sequencing analysis indicates trafficking between TDLNs and tumors and ongoing Tconv/Treg conversion. Overall, TDLN Tregs are functional and express a distinct pattern of druggable co-receptors, highlighting their potential as targets for cancer immunotherapy. Tumor-draining lymph nodes are often the first site of metastasis in breast cancer patients. Here, the authors show that metastatic lymph nodes are characterized by the accumulation of suppressive regulatory T cells with a distinct phenotype compared to matched non-invaded lymph nodes and tumors.
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