Brain-Resident MAIT Cells Infiltrate GL261 Tumors, and Activated MAIT Cell Signatures Are Associated With Improved Outcomes in Glioma.

Abstract

BACKGROUND AND OBJECTIVES: Mucosal-associated invariant T (MAIT) cells are unconventional T cells with emerging roles in antitumor immunity. Their phenotype in the brain and potential role in immunity to gliomas-including lower-grade (WHO grades I and II) and higher-grade gliomas such as grades III and IV (glioblastoma)-remain poorly defined. METHOD(S): We assessed the role of MAIT cells in glioma using publicly available transcriptomic data from patient cohorts. We then characterized MAIT cells in the mouse brain using flow cytometry and assessed their impact on survival and on other immune cells in the murine GL261 model of high-grade glioma. We tested previously developed methods to activate and expand MAIT cells in mice for their effect on brain MAIT cells. RESULT(S): Analysis of The Cancer Genome Atlas revealed an association between a gene signature of activated, but not naive, MAIT cells and improved survival in patients with grade III glioma. In mice, MAIT cells were predominantly brain-resident and infiltrated GL261 tumors where they produced IL-17 and IFN-gamma. Notably, MAIT cell-deficient Mr1-/- mice displayed reduced survival after GL261 tumor induction, suggesting a protective role for MAIT cells in higher grade gliomas. Injection of MAIT antigen and adjuvants expanded brain-resident MAIT cells, but expansion of MAIT cells alone prior to GL261 tumor induction did not significantly alter survival. DISCUSSION(S): Overall, this study supports a protective role for a population of brain-resident MAIT cells in glioma and highlights their potential involvement in immune surveillance of the CNS. Our findings also lay a foundation to explore the therapeutic modulation of MAIT cells in the brain.