期刊
NATURE COMMUNICATIONS
卷 12, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-21297-y
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资金
- Collaborative Research Program [SFB TR221]
- CRUK Career Development fellowship [C66259/A27114]
- Francis Crick Institute
- Cancer Research UK [FC001202]
- UK Medical Research Council [FC001202, MR/L016311/1]
- Wellcome Trust [747852-SIOMICS]
- KU Leuven [SymBioSys -C14/18/092]
- Foundation against Cancer [2015-143]
- Research Foundation Flanders [FWO I001818N]
- Research Foundation Flanders (FWO) [1S93320N]
- FWO [PEGASUS]2 Marie Sklodowska-Curie Fellowship [12O5617N]
- BBSRC [BB/P022073/1] Funding Source: UKRI
Regulatory T cells in breast cancer do not show clonal relationship with their circulating counterpart, but share a common origin with intratumoral antigen-experienced conventional T cells.
Regulatory CD4(+) T cells (Treg) prevent tumor clearance by conventional T cells (Tconv) comprising a major obstacle of cancer immune-surveillance. Hitherto, the mechanisms of Treg repertoire formation in human cancers remain largely unclear. Here, we analyze Treg clonal origin in breast cancer patients using T-Cell Receptor and single-cell transcriptome sequencing. While Treg in peripheral blood and breast tumors are clonally distinct, Tconv clones, including tumor-antigen reactive effectors (Teff), are detected in both compartments. Tumor-infiltrating CD4(+) cells accumulate into distinct transcriptome clusters, including early activated Tconv, uncommitted Teff, Th1 Teff, suppressive Treg and pro-tumorigenic Treg. Trajectory analysis suggests early activated Tconv differentiation either into Th1 Teff or into suppressive and pro-tumorigenic Treg. Importantly, Tconv, activated Tconv and Treg share highly-expanded clones contributing up to 65% of intratumoral Treg. Here we show that Treg in human breast cancer may considerably stem from antigen-experienced Tconv converting into secondary induced Treg through intratumoral activation. The mechanisms that shape the regulatory T cell repertoire in patients with cancer are not completely understood. Here, the authors observe that, in breast cancer patients, tumor-resident regulatory T cells do not show clonal relationship with their circulating counterpart, but share a common origin with intratumoral antigen-experienced conventional T cells.
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