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Dysfunctional tumor-infiltrating Vδ1 + T lymphocytes in microsatellite-stable colorectal cancer

Author

Listed:
  • Victoria Stary

    (Department of General Surgery, Division of Visceral Surgery, Comprehensive Cancer Center
    Institute for Hygiene and Applied Immunology)

  • Ram V. Pandey

    (Department of Dermatology)

  • Julia List

    (Department of General Surgery, Division of Visceral Surgery, Comprehensive Cancer Center)

  • Lisa Kleissl

    (Department of Dermatology)

  • Florian Deckert

    (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences)

  • Julijan Kabiljo

    (Department of General Surgery, Division of Visceral Surgery, Comprehensive Cancer Center)

  • Johannes Laengle

    (Department of General Surgery, Division of Visceral Surgery, Comprehensive Cancer Center)

  • Vasileios Gerakopoulos

    (Department of General Surgery, Division of Visceral Surgery, Comprehensive Cancer Center)

  • Rudolf Oehler

    (Department of General Surgery, Division of Visceral Surgery, Comprehensive Cancer Center)

  • Lukas Watzke

    (Department of Pathology)

  • Matthias Farlik

    (Department of Dermatology)

  • Samuel W. Lukowski

    (Dr. Boehringer Gasse 5-11)

  • Anne B. Vogt

    (Dr. Boehringer Gasse 5-11)

  • Georg Stary

    (Department of Dermatology
    CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences)

  • Hannes Stockinger

    (Institute for Hygiene and Applied Immunology)

  • Michael Bergmann

    (Department of General Surgery, Division of Visceral Surgery, Comprehensive Cancer Center)

  • Nina Pilat

    (Department of General Surgery, Division of Visceral Surgery, Comprehensive Cancer Center
    Department of Cardiac Surgery
    Center for Biomedical Research and Translational Surgery)

Abstract

Although γδ T cells are known to participate in immune dysregulation in solid tumors, their relevance to human microsatellite-stable (MSS) colorectal cancer (CRC) is still undefined. Here, using integrated gene expression analysis and T cell receptor sequencing, we characterized γδ T cells in MSS CRC, with a focus on Vδ1 + T cells. We identified Vδ1+ T cells with shared motifs in the third complementarity-determining region of the δ-chain, reflective of antigen recognition. Changes in gene and protein expression levels suggested a dysfunctional effector state of Vδ1+ T cells in MSS CRC, distinct from Vδ1+ T cells in microsatellite-instable (MSI). Interaction analysis highlighted an immunosuppressive role of fibroblasts in the dysregulation of Vδ1+ T cells in MSS CRC via the TIGIT-NECTIN2 axis. Blocking this pathway with a TIGIT antibody partially restored cytotoxicity of the dysfunctional Vδ1 phenotype. These results define an operative pathway in γδ T cells in MSS CRC.

Suggested Citation

  • Victoria Stary & Ram V. Pandey & Julia List & Lisa Kleissl & Florian Deckert & Julijan Kabiljo & Johannes Laengle & Vasileios Gerakopoulos & Rudolf Oehler & Lukas Watzke & Matthias Farlik & Samuel W. , 2024. "Dysfunctional tumor-infiltrating Vδ1 + T lymphocytes in microsatellite-stable colorectal cancer," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51025-1
    DOI: 10.1038/s41467-024-51025-1
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