ArticleThe Journal of clinical investigation2021
Inhibition of 2-hydroxyglutarate elicits metabolic reprogramming and mutant IDH1 glioma immunity in mice.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
96 citing papers in PubMed, 1 synthesis or guideline pooled it, 133 citations in OpenAlex.
- IDH mutation, glioma immunogenicity, and therapeutic challenge of primary mismatch repair deficient IDH-mutant astrocytoma PMMRDIA: a systematic review.Molecular oncology · 2024Pooled it
- Autophagy inhibition sensitizes radiotherapy responses in high-grade mutant IDH1 glioma.Nature communications · 2026Article
- Vorasidenib improves response to subsequent chemoradiation in a genetically engineered mouse model of IDH-mutant glioma.Science translational medicine · 2026Article
- Regulation of immune checkpoint molecules in cancer immune evasion and therapy.Nature reviews. Cancer · 2026Review
- Cancer stem cell plasticity: mechanisms, immune microenvironment crosstalk, and therapeutic implications.Journal of hematology & oncology · 2026Review
- Metabolic Reprogramming and Neurotransmitter Signaling Co-Option in the Glioma Immune Microenvironment: Dual-Axis Regulation of Immunosuppression.Biomolecules · 2026Review
- Reprogramming the immune suppressive tumor microenvironment in glioma enhances the efficacy of immune-mediated gene therapy.Molecular therapy. Oncology · 2026Article
- Brain Cancer: Molecular Alterations and Emerging Trends in Neuropharmacology.International journal of molecular sciences · 2026Review
- TP53 mutations in triple-negative breast cancer cells confer sensitivity to ASCT2 inhibition via arginine uptake.Cell death & disease · 2026Article
- Causal Pathways Linking Gut Microbiota, Serum Metabolites, and Meningioma Risk: A Mendelian Randomization Analysis.Brain and behavior · 2026Article
- Molecular mechanisms and clinical significance of the glioma metabolic-immune axis: a comprehensive review.Frontiers in immunology · 2026Review
- Bridging Discovery and Treatment: Cancer Biomarker.Cancers · 2025Review
- Metabolites as agents and targets for cancer immunotherapy.Nature reviews. Drug discovery · 2025Review
- UBE2T-Mediated HP1α Ubiquitination Enhances Nucleolar Function and Promotes the Progression of IDH1/TP53-Mutant Glioma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Autophagy Upregulation in Mutant Isocitrate Dehydrogenase 1 (IDH1) Glioma Uncovers a Novel Therapeutic Target.Research square · 2025Article
- Current Landscape of Preclinical Models for Pediatric Gliomas: Clinical Implications and Future Directions.Cancers · 2025Review
- Role of lysine acetylation-related genes in the diagnosis and prognosis of glioma.Scientific reports · 2025Article
- Advances in IDH-mutant glioma management: IDH inhibitors, clinical implications of INDIGO trial, and future perspectives.Future oncology (London, England) · 2025Review
- Review
- The role of vorasidenib in the treatment of isocitrate dehydrogenase-mutant glioma.Neuro-oncology · 2025Review
36 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 1 institution in 1 country.
Funding
Abstract
Mutant isocitrate dehydrogenase 1 (IDH1-R132H; mIDH1) is a hallmark of adult gliomas. Lower grade mIDH1 gliomas are classified into 2 molecular subgroups: 1p/19q codeletion/TERT-promoter mutations or inactivating mutations in α-thalassemia/mental retardation syndrome X-linked (ATRX) and TP53. This work focuses on glioma subtypes harboring mIDH1, TP53, and ATRX inactivation. IDH1-R132H is a gain-of-function mutation that converts α-ketoglutarate into 2-hydroxyglutarate (D-2HG). The role of D-2HG within the tumor microenvironment of mIDH1/mATRX/mTP53 gliomas remains unexplored. Inhibition of D-2HG, when used as monotherapy or in combination with radiation and temozolomide (IR/TMZ), led to increased median survival (MS) of mIDH1 glioma-bearing mice. Also, D-2HG inhibition elicited anti-mIDH1 glioma immunological memory. In response to D-2HG inhibition, PD-L1 expression levels on mIDH1-glioma cells increased to similar levels as observed in WT-IDH gliomas. Thus, we combined D-2HG inhibition/IR/TMZ with anti-PDL1 immune checkpoint blockade and observed complete tumor regression in 60% of mIDH1 glioma-bearing mice. This combination strategy reduced T cell exhaustion and favored the generation of memory CD8+ T cells. Our findings demonstrate that metabolic reprogramming elicits anti-mIDH1 glioma immunity, leading to increased MS and immunological memory. Our preclinical data support the testing of IDH-R132H inhibitors in combination with IR/TMZ and anti-PDL1 as targeted therapy for mIDH1/mATRX/mTP53 glioma patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.