Xydia, Maria and Rahbari, Raheleh and Ruggiero, Eliana and Macaulay, Iain and Tarabichi, Maxime and Lohmayer, Robert and Wilkening, Stefan and Michels, Tillmann and Brown, Daniel and Vanuytven, Sebastiaan and Mastitskaya, Svetlana and Laidlaw, Sean and Grabe, Niels and Pritsch, Maria and Fronza, Raffaele and Hexel, Klaus and Schmitt, Steffen and Mueller-Steinhardt, Michael and Halama, Niels and Domschke, Christoph and Schmidt, Manfred and von Kalle, Christof and Schuetz, Florian and Voet, Thierry and Beckhove, Philipp (2021) Common clonal origin of conventional T cells and induced regulatory T cells in breast cancer patients. NATURE COMMUNICATIONS, 12 (1): 1119. ISSN , 2041-1723
Full text not available from this repository. (Request a copy)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. The mechanisms that shape the regulatory T cell repertoire in patients with cancer are not completely understood. Here, the authors observe that, in breast cancer patients, tumor-resident regulatory T cells do not show clonal relationship with their circulating counterpart, but share a common origin with intratumoral antigen-experienced conventional T cells.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SINGLE CELLS; BONE-MARROW; RNA-SEQ; RECEPTOR; EXPRESSION; FOXP3; REPERTOIRE; EFFECTOR; SUBSETS; METHYLATION; |
| Subjects: | 500 Science > 530 Physics 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Zentren des Universitätsklinikums Regensburg > Regensburger Centrum für Interventionelle Immunologie (RCI) Physics > Institute of Theroretical Physics |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Sep 2022 06:52 |
| Last Modified: | 12 Sep 2022 06:52 |
| URI: | https://pred.uni-regensburg.de/id/eprint/47113 |
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