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

γδ T cells physiologically scan the intestinal epithelium, representing a substantial fraction of infiltrating lymphocytes in colorectal cancer (CRC), albeit their role in CRC remains unclear. Using murine CRC models, we found that most γδ T cells in pre- or non-tumor colon express Vγ1+ or Vγ7+ and exhibit a cytotoxic profile. Targeting these γδ T cell subsets, as well as conditionally interfering with γδ T cell function at early stages of tumorigenesis led to heightened tumor development, suggesting anti-CRC functions for Vγ1+ and Vγ7+ subsets. In contrast, RORγt+ γδ T cell subsets, including Vγ4+ and microbiotadependent Vγ6+, accumulated during CRC progression. Conditional deletion of RORγt or Vγ chains revealed redundant roles for IL-17–producing Vγ4+ and Vγ6+ γδ T cells in promoting tumor growth. Our results uncover pro- and anti-tumor roles for γδ T cell subsets. ### Competing Interest Statement The authors have declared no competing interest.