Role of MAIT cells in Glioblastoma

Glioblastoma (GBM) is the most aggressive primary brain cancer in adults and remains incurable. We used multi-omics and flow cytometry methods to investigate the role of mucosal-associated invariant T (MAIT) cells in GBM. In bulk RNA sequencing data analysis of GBM tissues, MAIT cell gene signature significantly correlated with poor patient survival. A scRNA-seq of CD45+ cells from 23 GBM tissue samples showed a diverse immune population in the GBM tumor microenvironment. Of the 23 GBM tissue samples analyzed, 15 (65.2%) were positive for MAIT cells. MAIT cells clustered with cell populations expressing a high level of transcription factor gene RORC, suggesting the enrichment of MAIT17 subset. The MAIT cell signature significantly correlated with the activity of tumor-associated neutrophils (TANs) and myeloid-derived suppressor cells (MDSCs). Multiple immune suppressive genes known to be used by TANs/MDSCs were upregulated in MAIT-positive tumors. Spatial imaging analysis of GBM tissues showed that all specimens were positive for both MAIT cells and TANs and localized enrichment of TANs. These findings highlight the MAIT-TAN/MDSC axis as a novel therapeutic target to modulate GBM’s immunosuppressive tumor microenvironment.