MAIT cell tumor infiltration predicts long-term survival in cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a malignancy arising from biliary epithelial cells of intra- and extra-hepatic bile ducts with dismal prognosis and few non-surgical treatments available. Despite recent success in the immunotherapy-based treatment of many tumor types, this has not been successfully translated to CCA. Mucosal associated invariant T (MAIT) cells are cytotoxic innate-like T cells highly enriched in human liver where they are located in close proximity to the biliary epithelium. Here, we aimed to comprehensively characterize MAIT cells in intrahepatic and perihilar CCA. Liver tissue from patients with CCA was used to study immune cells, including MAIT cells, in tumor-affected and surrounding tissue by immunohistochemistry, RNA sequencing, and multicolor flow cytometry. The intrahepatic and perihilar CCA tumor microenvironment was characterized by the presence of both cytotoxic T cells and high numbers of regulatory T cells. In contrast, MAIT cells were heterogenously lost from tumors compared to the surrounding liver tissue. This loss possibly occurred in response to increased bacterial burden within tumors. The residual intratumoral MAIT cell population exhibited phenotypic and transcriptomic alterations but a preserved receptor repertoire for interaction with tumor cells. Finally, high presence of MAIT cells in livers of intrahepatic CCA patients predicted long-term survival in two independent cohorts and was associated with a favourable anti-tumor immune signature. Conclusions: MAIT cell tumor-infiltration associates with favourable immunological fitness and predicts survival in cholangiocarcinoma.