Tissue-resident MAIT17 cells are associated with angiogenic pathways and tumor recurrence in non-small cell lung cancer (NSCLC) 3966

Abstract Description Interest in unconventional T cells in anti-tumor immunity is growing due to their established rapid effector functions, non-MHC-restricted nature, and unique ligand repertoire. Mucosal-associated invariant T cells (MAIT) are αβT cells that recognize non-peptide metabolites presented by MHC-related protein 1 (MR1) and can be activated independent of the TCR via cytokines. The role of MAIT cells in protecting the lung against bacterial and viral infections is well described, but their role in the human lung tumor microenvironment remains unclear. To investigate, surgical resections of tumor and normal adjacent tissue from treatment-naïve NSCLC patients were profiled using CITE-Seq and spectral flow cytometry. Distinct MAIT phenotypes were identified, including Th17-like (MAIT17) cells enriched for angiogenesis and tissue repair signatures, and Th1-like cells linked to cytotoxicity. Both subsets were significantly more activated in the tumor compared to matched normal adjacent tissue. Activated MAIT17 cells in normal adjacent tissue of ever-smokers was associated with greater tumor recurrence risk, and all T cell subsets showed increased IL17A production upon ex vivo stimulation, suggesting a global inflammatory response to smoking-induced tissue damage. These findings indicate a potentially pathogenic role for MAIT17 cells in driving tissue repair processes in normal adjacent lung tissue and propagating a tumor-promoting lung microenvironment even after tumor resection. Funding Sources Research is supported by the Canadian Institutes of Health Research (CIHR) Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)