%0 Journal Article
%T Dysfunctional tumor-infiltrating Vδ1 + T lymphocytes in microsatellite-stable colorectal cancer.
%A Stary V
%A Pandey RV
%A List J
%A Kleissl L
%A Deckert F
%A Kabiljo J
%A Laengle J
%A Gerakopoulos V
%A Oehler R
%A Watzke L
%A Farlik M
%A Lukowski SW
%A Vogt AB
%A Stary G
%A Stockinger H
%A Bergmann M
%A Pilat N
%J Nat Commun
%V 15
%N 1
%D 2024 Aug 13
%M 39138181
%F 17.694
%R 10.1038/s41467-024-51025-1
%X 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.