Advances in the Immunotherapeutic Potential of Isocitrate Dehydrogenase Mutations in Glioma

Abstract

Isocitrate dehydrogenase (IDH) is an essential metabolic enzyme in the tricarboxylic acid cycle (TAC). The high mutation frequency of the IDH gene plays a complicated role in gliomas. In addition to affecting gliomas directly, mutations in IDH can also alter their immune microenvironment and can change immune-cell function in direct and indirect ways. IDH mutations mediate immune-cell infiltration and function by modulating immune-checkpoint gene expression and chemokine secretion. In addition, IDH mutation-derived D2-hydroxyglutarate can be absorbed by surrounding immune cells, also affecting their functioning. In this review, we summarize current knowledge about the effects of IDH mutations as well as other gene mutations on the immune microenvironment of gliomas. We also describe recent preclinical and clinical data related to IDH-mutant inhibitors for the treatment of gliomas. Finally, we discuss different types of immunotherapy and the immunotherapeutic potential of IDH mutations in gliomas.

Keywords: Glioma; IDH mutation; Immunotherapy; Tumor immune microenvironment.