IM-1 THE IMMUNOSUPPRESSIVE ROLE OF MAIT CELLS AND MR1 IN GBM THROUGH THE INDUCTION OF NEUTROPHILS AND MDSCS

BACKGROUND: Glioblastoma (GBM) is a devastating brain tumor, and its immunosuppressive microenvironment has been implicated in the poor prognosis. However, the mechanism of the induction of the microenvironment is not well understood. MHC class I-related protein (MR1) is an antigen-presenting molecule for Mucosal-Associated Invariant T (MAIT) cells. Recently, MR1 transcriptomic level was reported to correlate with glioma’s poor survival, and the infiltration of MAIT cells in GBM was reported previously. However, the role of MAIT cells and MR1 in GBM is poorly understood. We aimed to understand the mechanism by which MR1 levels affect GBM patient survival and any potential involvement of MAIT cells. METHOD: RNA-sequencing data from TCGA-GBM was subjected to multi-layered analysis. Multiple methods, including comprehensive gene expression analysis and direct alignment-search using FASTQ data, were used to assess the immunological impact of MAIT cells in GBM. Using data from Pan-cancer TCGA, the role of MAIT cells in other cancer types was assessed. RESULT: The survival of GBM patients was negatively correlated with the level of MR1 expression. 8.3% of TCGA-GBM samples were identified to have MAIT cell infiltration, and the expression of MR1, the amount of MAIT cell infiltration, and the activity of tumor-associated neutrophils (TANs)/myeloid-derived suppressor cells (MDSCs) were significantly correlated. Simultaneously, the TAN/MDSC activity was significantly correlated with the poor survival of GBM patients. In four more cancer types, similar relationships between MAIT/MR1 and TANs/MDSCs were observed. CONCLUSIONS: Our observations shed light on the possible immunosuppressive role of MAIT cells and MR1. It was shown that MR1 up-regulation causes MAIT cell activation, which in turn causes TAN/MDSC induction. The current study implied the existence of a novel MAIT/MR1-TAN/MDSC immunosuppressive pathway, whose activation is associated with a worse prognosis for GBM. It was also suggested that a similar pathway might exist in other cancer types.