MAIT cells and MR1 play an immunosuppressive role in glioblastoma through the induction of neutrophils and MDSCs
Glioblastoma (GBM) is the most aggressive primary brain cancer in adults and remains incurable. Our study revealed an immunosuppressive 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 15 (65.2%) were positive for MAIT cells and the enrichment of MAIT17. 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 GBMs immunosuppressive tumor microenvironment.