TCR-Vγδ usage distinguishes pro- and anti-tumor intestinal γδ T cell subsets

γδ T cells represent a substantial fraction of intestinal lymphocytes at homeostasis, but also constitute a major lymphocyte population infiltrating colorectal cancers (CRC), albeit their role in CRC remains unclear. Using human CRC samples and murine CRC models, we found that most γδ T cells in pre- or non-tumor colon exhibit cytotoxic markers while tumor-infiltrating γδ T cells express a pro-tumorigenic profile. These contrasting T cell profiles were associated with distinct TCR-Vγδ gene-usage in both mice and humans. Complementary intersectional genetics and antibody-dependent strategies targeting murine γδ T cells enriched in the epithelium at steady state led to heightened tumor development, while targeting γδ subsets that accumulate during CRC resulted in reduced tumor growth. Our results uncover pro- and anti-tumor roles for γδ T cell subsets. Single Cells of Gamma Delta T cells of human patients (p337, p859, p989, p391, p633) sorted from healthy (N) and colon rectal cancer (T) areas; libraries are the antibody derived tags, gene expression and tcr sequencing. Bulk RNA-Seq of sorted CD8a+PD-1- and CD8a-PD-1+ Gamma Delta T cells, extracted from colon tumors of mice in triplicates.