The immunological landscape of IDH-mutant gliomas is characterized by distinct myeloid cell states that are influenced by the tumor genotype. A study employing longitudinal single-cell profiling revealed that in IDH-mutant gliomas, the differentiation of infiltrating myeloid cells is impeded, leading to an immature phenotype that contributes to a suppressive tumor microenvironment. This is particularly evident in late-stage gliomas, where monocyte-derived macrophages promote a tolerogenic microenvironment, effectively inhibiting T cell responses (ref: Friedrich doi.org/10.1038/s43018-021-00201-z/). Furthermore, the metabolic byproduct 2-hydroxyglutarate (2HG), produced by mutant IDH, has been identified as a potential barrier to immunotherapeutic strategies, complicating the treatment landscape for these patients (ref: Richardson doi.org/10.3171/2021.11.FOCUS21604/). In vivo experiments demonstrated that decitabine can enhance natural killer (NK) cell-mediated responses against IDH-mutant gliomas, suggesting a potential therapeutic avenue that could overcome some of the immunosuppressive effects (ref: Zhang doi.org/10.3171/2021.11.FOCUS21489/). Additionally, bioinformatic analyses have identified immune checkpoint inhibitor targets in gliomas, highlighting the need for tailored immunotherapeutic approaches based on tumor genetics (ref: Ding doi.org/10.1155/2022/).

The metabolic profiles of gliomas, particularly those classified by the WHO, reveal significant differences that could inform therapeutic strategies. A comprehensive metabolomic analysis of 224 glioma samples identified distinct metabolic hallmarks that differentiate between oligodendrogliomas, astrocytomas, and glioblastomas, suggesting that these metabolic features could be leveraged for improved diagnostics and targeted therapies (ref: Björkblom doi.org/10.1093/neuonc/). However, the efficacy of dietary interventions, such as a ketogenic diet, was found to be limited in preclinical models of both IDH wild-type and mutant gliomas, indicating that metabolic manipulation alone may not suffice to alter tumor growth dynamics (ref: Javier doi.org/10.1371/journal.pone.0257725/). Moreover, the regulation of mutant IDH1 and IDH2 by the mitotic kinase Plk1 underscores the complex interplay between metabolic pathways and cell cycle regulation, which could present new therapeutic targets (ref: Saikiran Reddy doi.org/10.1016/j.cellsig.2022.110279/). A retrospective study on oligodendrogliomas also highlighted the role of the phosphatidylinositol 3-kinase pathway in tumor progression, emphasizing the need for a multifaceted approach to treatment (ref: Dono doi.org/10.1227/neu.0000000000001875/).

Advancements in imaging techniques are enhancing the diagnostic capabilities for gliomas, particularly lower-grade gliomas (LGGs). Preoperative [11C]methionine PET has been shown to effectively assess molecular features and predict prognosis in LGGs, thereby aiding in personalized treatment decisions (ref: Ninatti doi.org/10.1093/neuonc/). Additionally, a systematic review and meta-analysis of the T2-FLAIR mismatch sign indicated that while it is not a sensitive indicator for IDH mutation status, it does exhibit high specificity for certain subtypes, which could refine diagnostic accuracy (ref: Han doi.org/10.1007/s00330-022-08607-8/). Radiomics models incorporating qualitative features have demonstrated improved predictive capabilities for molecular subtypes in LGGs, achieving balanced accuracies that underscore the potential of integrating advanced imaging with clinical data (ref: Sun doi.org/10.3389/fonc.2021.756828/). Furthermore, diffusion MRI using a gamma distribution model has shown promise in differentiating IDH-mutant from IDH-wildtype glioblastomas, indicating that diffusion metrics can provide valuable insights into tumor pathology (ref: Takase doi.org/10.1259/bjr.20210392/). Innovations such as terahertz spectroscopy are also being explored for rapid molecular pathological recognition of gliomas, highlighting the ongoing evolution of diagnostic modalities in neuro-oncology (ref: Mu doi.org/10.1364/BOE.445111/).

The molecular pathology of gliomas is increasingly recognized as a critical determinant of prognosis and treatment response. Bioinformatic analyses have identified immune checkpoint inhibitor targets that correlate with IDH mutation status, suggesting that molecular profiling could guide therapeutic decisions in glioma management (ref: Ding doi.org/10.1155/2022/). Notably, high expression of the Duchenne muscular dystrophy gene (DMD) has emerged as an independent prognostic marker in IDH-mutant low-grade gliomas, with significant implications for overall survival, indicating that molecular markers can provide insights into patient outcomes (ref: Naidoo doi.org/10.1038/s41598-022-07223-2/). Additionally, the association of T2 FLAIR hyperintensity volumes with cognitive function and quality of life in stable lower-grade glioma patients highlights the importance of considering neurocognitive outcomes alongside traditional survival metrics (ref: Luks doi.org/10.3389/fneur.2021.769345/). Furthermore, the upregulation of TERT expression with tumor grade suggests a role in tumor progression and senescence evasion, warranting further investigation into its potential as a therapeutic target (ref: Jalasutram null).