Comparative profiling of MAIT cells across gastrointestinal cancers identifies conserved NK receptor dysregulation and HCC-specific defects in cytotoxicity and XBP1s signaling

Background & aims: Mucosal-associated invariant T (MAIT) cells are innate-like T lymphocytes with cytotoxic capacity and emerging roles in tumour immunity. While MAIT cells express a diverse repertoire of natural killer (NK) receptors, the functional significance of these receptors in gastrointestinal (GI) cancers remains poorly understood.

Methods

We characterized the NK receptor repertoire and effector function of MAIT cells across five human GI tumour entities: hepatocellular carcinoma (HCC; n = 30), colorectal liver metastases (CRLM; n = 15), colorectal cancer (CRC; n = 17), pancreatic ductal adenocarcinoma (PDAC; n = 17), and gastric cancer (GC; n = 18), and examined the functional phenotype and cytotoxic potential of primary HCC-derived MAIT cells.