Researchers discover how bowel cancer 'blinds' the immunesystem
Intraepithelial lymphocytes expressing γδ T-cell receptors play key roles in elimination of colon cancer. However, the precise mechanisms by which progressing cancer cells evade immunosurveillance by these innate T cells are unknown. Here, we investigated how loss of the Apc tumor suppressor in gut tissue could enable nascent cancer cells to escape immunosurveillance by cytotoxic γδIELs.
We then demonstrated that β-catenin activation through loss of Apc rapidly suppressed expression of the mRNA encoding the HNF4A and HNF4G transcription factors, preventing their binding to promoter regions of Btnl genes. Re-expression of BTNL1 and BTNL6 in cancer cells increased γδIEL survival and activation in co-culture assays but failed to augment their cancer-killing ability in vitro or their recruitment to orthotopic tumors.
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