Implications of IDH mutations on immunotherapeutic strategies for malignant glioma

• Main Authors: Choi, B.D (Author), Curry, W.T (Author), Kitagawa, Y. (Author), Miller, J.J (Author), Richardson, L.G (Author), Wakimoto, H. (Author)
• Format: Article
• Language: English
• Published: American Association of Neurological Surgeons 2022
• Subjects: 2-hydroxyglutarate; Brain Neoplasms; brain tumor; genetics; glioma; Glioma; human; Humans; IDH; immunology; immunosuppression; immunotherapy; Immunotherapy; isocitrate dehydrogenase; Isocitrate Dehydrogenase; metabolism; mutation; Mutation; tumor immune microenvironment; tumor microenvironment; Tumor Microenvironment
• Online Access: View Fulltext in Publisher

 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. © 2022 AANS. All Rights Reserved.