Unconventional guardians of the brain: MAIT cells as emerging players in glioblastoma immunity

Glioblastomas (GBM) are an aggressive form of brain cancer with no curative treatment options. While T cell therapies have demonstrated substantial success in combatting blood cancers, their application for solid tumours, including GBM, is hampered by the immunosuppressive tumour microenvironment and scarcity of tumour antigen-specific targets. There is an urgent need to better understand the immune response to GBM to enable the development of new therapeutic approaches. Recently, a resident population of mucosal-associated invariant T (MAIT) cells in the brain has been described, which may perform critical immune surveillance functions. Recent research also suggests that MAIT cells play diverse roles in anti-tumour immunity, and there is much interest in exploring the potential of MAIT cells in immune therapy by harnessing their cytotoxic capacity and tissue homing properties. However, findings on the role of MAIT cells in cancer are conflicting, while many basic questions regarding MAIT-tumour cell interactions remain. Here we review the challenges for GBM treatment, as well as the potential of unconventional T cells in cancer immunotherapy, with a focus on MAIT cells, their potential role in cancer, and their suitability as novel therapeutic targets in solid tumours such as GBM.