Common clonal origin of conventional T cells and induced regulatory T cells in breast cancer patients
Publication Year 2021-02-18, Volume 12, Issue #1, Page 1119
Journal Title
Nature Communications
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.
WEHI Research Division(s)
Advanced Technology And Biology
PubMed ID
Open Access at Publisher's Site
Rights Notice
Refer to copyright notice on published article.

Creation Date: 2021-03-09 01:37:10
Last Modified: 2021-03-09 03:01:55
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