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. Overall design: The GBM patient cohort comprised nine patients newly diagnosed with GBM, seven patients with recurrent GBM who have not been treated with any immunotherapy, and seven recurrent GBM patients who were treated with neoadjuvant anti-PD1 therapy. CD45+ cells isolated from the GBM patients' tumor were used to perform scRNA-seq and scTCR-seq exeriments.