Implications of IDH mutations on immunotherapeutic strategies for malignant glioma

Immunotherapy has emerged as a promising approach for treating aggressive solid tumors, even within the CNS. Mutation in the metabolic gene isocitrate dehydrogenase 1 (IDH1) represents not only a major glioma defining biomarker but also an attractive therapeutic neoantigen. As patients with IDH-mutant glioma enter early-phase vaccine and immune checkpoint inhibitor clinical trials, there is emerging evidence that implicates the oncometabolite, 2-hydroxyglutarate (2HG), generated by the neomorphic activity of mutant IDH, as a potential barrier to current immunotherapeutic approaches. Here, the authors review the immunomodulatory and immunosuppressive roles of 2HG within the unique IDH-mutant glioma tumor immune microenvironment and discuss promising immunotherapeutic approaches currently being investigated in preclinical models.

Automated summary

Immunotherapy has shown promising potential in treating aggressive solid tumors, including those within the central nervous system. However, the presence of the oncometabolite 2-hydroxyglutarate (2HG) generated by mutant IDH has been identified as a potential barrier to current immunotherapeutic approaches.