Isocitrate dehydrogenase (IDH) is an essential metabolic enzyme in the tricarboxylic acid cycle (TAC). The high mutation frequency of the IDH gene plays a complicated role in gliomas. In addition to affecting gliomas directly, mutations in IDH can also alter their immune microenvironment and can change immune-cell function in direct and indirect ways. IDH mutations mediate immune-cell infiltration and function by modulating immune-checkpoint gene expression and chemokine secretion. In addition, IDH mutation-derived D2-hydroxyglutarate can be absorbed by surrounding immune cells, also affecting their functioning. In this review, we summarize current knowledge about the effects of IDH mutations as well as other gene mutations on the immune microenvironment of gliomas. We also describe recent preclinical and clinical data related to IDH-mutant inhibitors for the treatment of gliomas. Finally, we discuss different types of immunotherapy and the immunotherapeutic potential of IDH mutations in gliomas.
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http://dx.doi.org/10.1007/s12264-022-00866-1 | DOI Listing |
Front Oncol
January 2025
Department of Pediatric and Adolescent Oncology/Hematology, Perth Children's Hospital, Nedlands, WA, Australia.
Gliomas account for nearly 30% of all primary central nervous system (CNS) tumors in children and adolescents and young adults (AYA), contributing to significant morbidity and mortality. The updated molecular classification of gliomas defines molecularly diverse subtypes with a spectrum of tumors associated with age-distinct incidence. In adults, gliomas are characterized by the presence or absence of mutations in isocitrate dehydrogenase (), with mutated (mIDH) gliomas providing favorable outcomes and avenues for targeted therapy with the emergence of mIDH inhibitors.
View Article and Find Full Text PDFSci Rep
January 2025
Shanghai Key Laboratory of Magnetic Resonance, School of Physics and Electronic Science, East China Normal University, Shanghai, China.
Prediction of isocitrate dehydrogenase (IDH) mutation status and epilepsy occurrence are important to glioma patients. Although machine learning models have been constructed for both issues, the correlation between them has not been explored. Our study aimed to exploit this correlation to improve the performance of both of the IDH mutation status identification and epilepsy diagnosis models in patients with glioma II-IV.
View Article and Find Full Text PDFComput Biol Med
January 2025
Institute of Biomedical Engineering, Bogazici University, Istanbul, Turkey; Center for Neuroradiological Applications and Research, Acibadem University, Istanbul, Turkey.
Background: Preoperative and noninvasive detection of isocitrate dehydrogenase (IDH) and telomerase reverse transcriptase gene promoter (TERTp) mutations in glioma is critical for prognosis and treatment planning. This study aims to develop deep learning classifiers to identify IDH and TERTp mutations using proton magnetic resonance spectroscopy (H-MRS) and a one-dimensional convolutional neural network (1D-CNN) architecture.
Methods: This study included H-MRS data from 225 adult patients with hemispheric diffuse glioma (117 IDH mutants and 108 IDH wild-type; 99 TERTp mutants and 100 TERTp wild-type).
Life Metab
April 2024
State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
Isocitrate dehydrogenase (IDH) mutations frequently occur in lower-grade gliomas and secondary glioblastomas. Mutant IDHs exhibit a gain-of-function activity, leading to the production of D-2-hydroxyglutarate (D-2HG) by reducing α-ketoglutarate (α-KG), a central player in metabolism and epigenetic modifications. However, the role of α-KG homeostasis in IDH-mutated gliomagenesis remains elusive.
View Article and Find Full Text PDFFront Oncol
January 2025
Shanghai Institute of Precision Medicine, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Introduction: The Wnt/planar cell polarity (PCP) signaling pathway is pivotal in regulating various biological processes such as early embryonic development, neural crest cell migration, and cancer invasion. Despite advances in understanding the role of Wnt/PCP pathway dysregulation in tumorigenesis, numerous unanswered questions remain. Our study focused on VANGL2, a core PCP gene, to elucidate its potential mechanistic involvement in cancer development.
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