Perspectives of immunotherapy in isocitrate dehydrogenase-mutant gliomas

• Verfasst von: Friedrich, Mirco [VerfasserIn]
• Verfasst von: Bunse, Lukas [VerfasserIn]
• Verfasst von: Wick, Wolfgang [VerfasserIn]
• Verfasst von: Platten, Michael [VerfasserIn]
• Titel: Perspectives of immunotherapy in isocitrate dehydrogenase-mutant gliomas
• Verf.angabe: Mirco Friedrich, Lukas Bunse, Wolfgang Wick, and Michael Platten
• Jahr: 2018
• Umfang: 7 S.
• Fussnoten: Gesehen am 25.07.2019 ; Doi funktioniert nicht
• Titel Quelle: Enthalten in: Current opinion in oncology
• Ort Quelle: Philadelphia, Pa. : Lippincott Williams & Wilkins, 1989
• Jahr Quelle: 2018
• Band/Heft Quelle: 30(2018), 6, Seite 368-374
• ISSN Quelle: 1531-703X
• DOI: doi:10.1097/CCO.0000000000000478
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 167003187X

Abstract

Purpose of review The present review introduces recent progress in eliciting the role of mutant isocitrate dehydrogenase (IDH) in gliomas, especially regarding its mode of action as a modulator of antitumor immune response, and provides rationales for targeting mutant IDH in glioma immunotherapy. Both the development of small molecule inhibitors repressing the enzymatic activity of mutant IDH and novel, mechanism-led combination immunotherapies are discussed. - Recent findings Since the discovery of highly frequent IDH mutations in low-grade gliomas and nonsolid malignancies, its tumor cell-intrinsic effects have been intensively investigated. Tumor cells expressing mutant IDH display profound alterations of redox control capacity, phospholipid profile, and ATP supply. Recent findings suggest that IDH mutations - via intricate, yet druggable pathways - cause immunological alterations, highlighting the importance of oncogenic drivers as modulators of antitumor immunity and targets for immunotherapy. - Summary Mutant IDH is not only a disease-defining biomarker and oncogenic driver in glioma, but is also a neoantigen and a regulator of glioma immune evasion. Effective and specific strategies targeting the immunomodulatory properties of mutant IDH may complement current (immuno-)therapeutic strategies and approved antiglioma treatments to improve outcome.