{Reference Type}: Journal Article
{Title}: Dysfunctional tumor-infiltrating Vδ1 + T lymphocytes in microsatellite-stable colorectal cancer.
{Author}: Stary V;Pandey RV;List J;Kleissl L;Deckert F;Kabiljo J;Laengle J;Gerakopoulos V;Oehler R;Watzke L;Farlik M;Lukowski SW;Vogt AB;Stary G;Stockinger H;Bergmann M;Pilat N;
{Journal}: Nat Commun
{Volume}: 15
{Issue}: 1
{Year}: 2024 Aug 13
{Factor}: 17.694
{DOI}: 10.1038/s41467-024-51025-1
{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.