Common clonal origin of conventional T cells and induced regulatory T cells in breast cancer patients
Details
Publication Year 2021-02-18, Volume 12, Issue #1, Page 1119
Journal Title
Nature Communications
Abstract
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.
Publisher
NPG
WEHI Research Division(s)
Advanced Technology And Biology
PubMed ID
33602930
Open Access at Publisher's Site
https://doi.org/10.1038/s41467-021-21297-y
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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