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, Mueller-Steinhardt M, Halama N, Domschke C, Schmidt M, Von Kalle C, Schuetz F, Voet T, Beckhove P (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Nature Communications Nature Publishing Group: Nature Communications

Book Volume: 12

Article Number: 1119

Journal Issue: 1

DOI: 10.1038/s41467-021-21297-y

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.

Involved external institutions

Universitätsklinikum Regensburg DE Germany (DE) Wellcome Trust Sanger Institute - Genome Research Limited GB United Kingdom (GB) Deutsches Krebsforschungszentrum (DKFZ) DE Germany (DE) Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven BE Belgium (BE) The Francis Crick Institute GB United Kingdom (GB) Ruprecht-Karls-Universität Heidelberg DE Germany (DE) Universitätsklinikum Heidelberg DE Germany (DE)

How to cite

APA:

Xydia, M., Rahbari, R., Ruggiero, E., Macaulay, I., Tarabichi, M., Lohmayer, R.,... Beckhove, P. (2021). Common clonal origin of conventional T cells and induced regulatory T cells in breast cancer patients. Nature Communications, 12(1). https://doi.org/10.1038/s41467-021-21297-y

MLA:

Xydia, Maria, et al. "Common clonal origin of conventional T cells and induced regulatory T cells in breast cancer patients." Nature Communications 12.1 (2021).

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