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

Nature Communications, ISSN: 2041-1723, Vol: 12, Issue: 1, Page: 1119
2021
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Article Description

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.

Bibliographic Details

Xydia, Maria; Rahbari, Raheleh; Ruggiero, Eliana; Macaulay, Iain; Tarabichi, Maxime; Lohmayer, Robert; Wilkening, Stefan; Michels, Tillmann; Brown, Daniel; Vanuytven, Sebastiaan; Mastitskaya, Svetlana; Laidlaw, Sean; Grabe, Niels; Pritsch, Maria; Fronza, Raffaele; Hexel, Klaus; Schmitt, Steffen; Müller-Steinhardt, Michael; Halama, Niels; Domschke, Christoph; Schmidt, Manfred; von Kalle, Christof; Schütz, Florian; Voet, Thierry; Beckhove, Philipp

Springer Science and Business Media LLC

Chemistry; Biochemistry, Genetics and Molecular Biology; Physics and Astronomy

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