Potential of IDH mutations as immunotherapeutic targets in gliomas: a review and meta-analysis

Abstract

Introduction: Gliomas are stratified by the presence of a hotspot mutation in the enzyme isocitrate dehydrogenase genes (IDH1/2). While mutated IDH (mIDH) correlates with better prognosis, the role of this mutation in antitumor immunity and the response to immunotherapy is not completely understood. Understanding the relationship between the genetic features of these tumors and the tumor immune microenvironment (TIME) may help to develop appropriate therapeutic strategies. Areas covered: In this review we discussed the available literature related to the potential role of IDH mutations as an immunotherapeutic target in gliomas and profiled the immune transcriptome of glioma biopsies. We aimed to shed light on the role of mIDH on the immunological landscape of the different subtypes of gliomas, taking into account the most recent WHO classification of tumors of the central nervous system (CNS). We also discussed different immunotherapeutic approaches to target mIDH tumors and to overcome their immunosuppressive microenvironment. Expert opinion: Data presented here indicates that the TIME not only differs in association with IDH mutation status, but also within glioma subtypes, suggesting that the cellular context affects the overall effect of this genetic lesion. Thus, specific therapeutic combinations may help patients diagnosed with different glioma subtypes.