Common clonal origin of conventional T cells and induced regulatory T cells in breast cancer patients

Xydia, M; Rahbari, R; Ruggiero, E; Macaulay, I; Tarabichi, M; Lohmayer, R; Wilkening, S; Michels, T; Brown, D; Vanuytven, S; Mastitskaya, S; Laidlaw, S; Grabe, N; Pritsch, M; Fronza, R; Hexel, K; Schmitt, S; M&#252;ller-Steinhardt, M; Halama, N; Domschke, C; Schmidt, M; von Kalle, C; Sch&#252;tz, F; Voet, T; Beckhove, P

Author(s): Xydia, M; Rahbari, R; Ruggiero, E; Macaulay, I; Tarabichi, M; Lohmayer, R; Wilkening, S; Michels, T; Brown, D; Vanuytven, S; Mastitskaya, S; Laidlaw, S; Grabe, N; Pritsch, M; Fronza, R; Hexel, K; Schmitt, S; Müller-Steinhardt, M; Halama, N; Domschke, C; Schmidt, M; von Kalle, C; Schütz, F; Voet, T; Beckhove, P;
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
Research Division(s): Advanced Technology And Biology
PubMed ID: 33602930
Publisher's Version: https://doi.org/10.1038/s41467-021-21297-y
Open Access at Publisher's Site: https://doi.org/10.1038/s41467-021-21297-y
Terms of Use/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