T cell exhaustion in malignant gliomas

Gliomas remain notoriously difficult to treat and the use of immunotherapy to treat CNS cancers has been far less successful than in other cancer types.T cell exhaustion is defined by reduced proliferative capacity, reduced production of effector cytokines, sustained expression of inhibitory receptors, altered transcriptional and epigenetic states, and impaired metabolic activity.The glioma microenvironment contains distinct factors that drive T cell exhaustion and dysfunctional metabolic states.Metabolic and microenvironmental alterations have unique impacts on the epigenetic and transcriptional changes that drive T cell exhaustion in gliomas.Reversal of T cell exhaustion has the potential to enhance antitumor immunity and treatment efficacy in malignant gliomas.