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

ABSTRACT: 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.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE205720 | GEO | 2022/06/14

REPOSITORIES: GEO

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

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