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

GONZALEZ, NAZARENO; ASAD, ANTONELA S.; GÓMEZ ESCALANTE, JOSÉ; PEÑA AGUDELO, JORGE A.; NICOLA CANDIA, ALEJANDRO J.; GARCÍA FALLIT, MATÍAS; SEILICOVICH, ADRIANA; CANDOLFI, MARIANELA

EXPERT OPINION ON THERAPEUTIC TARGETS

INFORMA HEALTHCARE

Año: 2021 vol. 25 p. 1045 - 1060

1472-8222

ABSTRACTIntroduction: Gliomas are stratified by the presence of a hotspot mutation in the enzyme isocitratedehydrogenase 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 discuss the available literature related to the potential role of IDHmutations as an immunotherapeutic target in gliomas and profiled the immune transcriptome ofglioma biopsies. We aimed to shed light on the role of mIDH on the immunological landscape of thedifferent subtypes of gliomas, taking into account the most recent WHO classification of tumors of the central nervous system (CNS). We also discuss 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 IDHmutation 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.