Vγ usage distinguishes pro- and anti-tumor intestinal γδ T cell subsets
Reis, B. S.; Darcy, P. W.; Khan, I. Z.; Eleso, O.; Zhu, C.; Schernthanner, M.; Lockhart, A.; Reed, A.; Bortolatto, J.; Castro, T.; Bilate, A.; Grivennikov, S.; Mucida, D.
Show abstract
{gamma}{delta} 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 {gamma}{delta} T cells in pre- or non-tumor colon express V{gamma}1+ or V{gamma}7+ and exhibit a cytotoxic profile. Targeting these {gamma}{delta} T cell subsets, as well as conditionally interfering with {gamma}{delta} T cell function at early stages of tumorigenesis led to heightened tumor development, suggesting anti-CRC functions for V{gamma}1+ and V{gamma}7+ subsets. In contrast, ROR{gamma}t+ {gamma}{delta} T cell subsets, including V{gamma}4+ and microbiotadependent V{gamma}6+, accumulated during CRC progression. Conditional deletion of ROR{gamma}t or V{gamma} chains revealed redundant roles for IL-17-producing V{gamma}4+ and V{gamma}6+ {gamma}{delta} T cells in promoting tumor growth. Our results uncover pro- and anti-tumor roles for {gamma}{delta} T cell subsets.
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