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

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. Lukowski, Anne B. Vogt, Georg Stary, Hannes Stockinger, Michael Bergmann and Nina Pilat
Additional contact information
Victoria Stary: Department of General Surgery, Division of Visceral Surgery, Comprehensive Cancer Center
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
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

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: 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.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-51025-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51025-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-51025-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().