Th80 - The Role of Mucosal-Associated Invariant T (MAIT) Cells in Glioblastoma Immunity

Thursday, June 23, 2022

6:15 PM – 7:30 PM PT

Presenting Author(s)

TH

Taijun Hana, MD, PhD

Visiting fellow
National Cancer Institute, National Institutes of Health
North Bethesda, Maryland, United States

Co-Author(s)

MT

Masaki Terabe, PhD

Investigator
National Cancer Institute, National Institutes of Health
Bethesda, Maryland, United States

Glioblastoma (GBM) is a devastating disease, and its 5-year survival rate is approximately 10%. Immunotherapies have not been shown to be effective against GBM, so a better understanding of GBM immunity is needed. Mucosal-Associated Invariant T (MAIT) cells are MHC class I related-1 molecule (MR1)-restricted T cells and regulate tumor immunity. Although MAIT cells were reported to exist in GBM tissue, their roles are unknown. We examined their function in GBM. Since MAITs’ T cell receptors (TCRs) use limited combinations of gene segments, we searched the characteristic sequence combinations in the TCGA-GBM transcriptomic data and calculated the MAIT cell infiltration levels (MIL). Results showed that 8.6% of samples were MAIT positive, and immune-suppressive genes were up-regulated in those positive samples. There was no appropriate method available to study co-expressing genes with MIL comprehensively. Thus, by taking advantage of our observation of a significant correlation between MIL and MR1 gene expression (r = 0.22, p = 0.0045), we extracted all genes highly co-expressing with MR1. The tumor-immunosuppressive “Neutrophil degranulation (ND)” pathway was enriched in those genes. The genes sorted into this pathway contributed to the exocytosis of Arginase 1 (Arg1), which can impair T cell functions. It was also confirmed that 90% of those genes and Arg1 co-expressed with MIL, and all the detected ND-related genes and Arg1 tended to inversely correlate with the patient survival. Our study suggested that infiltrated MAIT cells in GBM may suppress tumor immunity by activating ND and Arg1 release.