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

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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    Cited by:

    1. Samar Elorbany & Chiara Berlato & Larissa S. Carnevalli & Eleni Maniati & Simon T. Barry & Jun Wang & Ranjit Manchanda & Julia Kzhyshkowska & Frances Balkwill, 2024. "Immunotherapy that improves response to chemotherapy in high-grade serous ovarian cancer," Nature Communications, Nature, vol. 15(1), pages 1-20, December.

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