Author
Listed:
- Maria Xydia
(University and Department of Hematology/Oncology, University Medical Centre of Regensburg
German Cancer Research Centre)
- Raheleh Rahbari
(Wellcome Sanger Institute)
- Eliana Ruggiero
(National Centre for Tumor Diseases and German Cancer Research Centre)
- Iain Macaulay
(Wellcome Sanger Institute
Earlham Institute)
- Maxime Tarabichi
(Wellcome Sanger Institute
The Francis Crick Institute)
- Robert Lohmayer
(University and Department of Hematology/Oncology, University Medical Centre of Regensburg
University of Regensburg)
- Stefan Wilkening
(National Centre for Tumor Diseases and German Cancer Research Centre)
- Tillmann Michels
(University and Department of Hematology/Oncology, University Medical Centre of Regensburg)
- Daniel Brown
(University of Leuven, KU Leuven
The Walter and Eliza Hall Institute of Medical Research)
- Sebastiaan Vanuytven
(The Francis Crick Institute
University of Leuven, KU Leuven)
- Svetlana Mastitskaya
(National Centre for Tumor Diseases
University College London)
- Sean Laidlaw
(Wellcome Sanger Institute)
- Niels Grabe
(National Centre for Tumor Diseases
University of Heidelberg)
- Maria Pritsch
(German Cancer Research Centre)
- Raffaele Fronza
(National Centre for Tumor Diseases and German Cancer Research Centre)
- Klaus Hexel
(German Cancer Research Centre)
- Steffen Schmitt
(German Cancer Research Centre)
- Michael Müller-Steinhardt
(Medical Faculty Mannheim, Heidelberg University)
- Niels Halama
(National Centre for Tumor Diseases
University of Heidelberg)
- Christoph Domschke
(University Hospital of Heidelberg)
- Manfred Schmidt
(National Centre for Tumor Diseases and German Cancer Research Centre)
- Christof von Kalle
(National Centre for Tumor Diseases and German Cancer Research Centre
Clinical Study Centre, Charité/BIH)
- Florian Schütz
(University Hospital of Heidelberg)
- Thierry Voet
(Wellcome Sanger Institute
University of Leuven, KU Leuven)
- Philipp Beckhove
(University and Department of Hematology/Oncology, University Medical Centre of Regensburg
German Cancer Research Centre)
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.
Suggested Citation
Maria Xydia & Raheleh Rahbari & Eliana Ruggiero & Iain Macaulay & Maxime Tarabichi & Robert Lohmayer & Stefan Wilkening & Tillmann Michels & Daniel Brown & Sebastiaan Vanuytven & Svetlana Mastitskaya , 2021.
"Common clonal origin of conventional T cells and induced regulatory T cells in breast cancer patients,"
Nature Communications, Nature, vol. 12(1), pages 1-18, December.
Handle:
RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21297-y
DOI: 10.1038/s41467-021-21297-y
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