ArticleOncoimmunology
D-2-hydroxyglutarate interferes with HIF-1α stability skewing T-cell metabolism towards oxidative phosphorylation and impairing Th17 polarization.
Article in Oncoimmunology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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Who cites it
84 citing papers in PubMed, 124 citations in OpenAlex.
- Resolving challenges in detection and quantification of D-2-hydroxyglutarate and L-2-hydroxyglutarate via LC/MS.Methods (San Diego, Calif.) · 2026Article
- Rewiring tumor metabolism: heterogeneity, oncometabolites, and adaptive plasticity.Experimental hematology & oncology · 2026Review
- A new perspective on mesenchymal stem cells and their derivatives in alleviating cerebral ischemia-reperfusion injury dynamically regulating mitochondrial function to remodel the immune network.Cell death & disease · 2026Review
- Multiomics-guided discovery of protective microbiome signatures in lupus-prone mice treated with Faecalibacterium prausnitzii.Nature communications · 2026Article
- IDH1 Mutant Glioma Favors Group 3 Innate Lymphoid Cells and Is Resistant to Immune Checkpoint Expression.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Single-cell genomics highlight MYC-associated metabolic activation and altered cell interactions in T-prolymphocytic leukemia progression.Nature communications · 2026Article
- <p>Regulatory networks of HIFs in tumor‑infiltrating immune cells: From molecular mechanisms to therapeutic implications (Review)</p>.International journal of oncology · 2026Review
- Targeting metabolic-epigenetic-immune axis in cancer: molecular mechanisms and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- Regulation of CD4 + T cell differentiation and function by glucose metabolism.Genes and immunity · 2025Review
- Immunometabolism of regulatory T cells in cancer.Oncogene · 2025Review
- Targeting CD4+ T Cell Glucose Metabolism: A Novel Immunotherapeutic Approach for Type 1 Diabetes.Biomolecules · 2025Review
- Metabolic Reprogramming in Response to Freund's Adjuvants: Insights from Serum Metabolomics.Microorganisms · 2025Article
- The Role and Applied Value of Mitochondria in Glioma-Related Research.CNS neuroscience & therapeutics · 2024Review
- Review
- Article
- Both Enantiomers of 2-Hydroxyglutarate Modulate the Metabolism of Cultured Human Neuroblastoma Cells.Neurochemical research · 2024Article
- Tricarboxylic Acid Cycle Relationships with Non-Metabolic Processes: A Short Story with DNA Repair and Its Consequences on Cancer Therapy Resistance.International journal of molecular sciences · 2024Review
- Divergent Processing of Cell Stress Signals as the Basis of Cancer Progression: Licensing NFκB on Chromatin.International journal of molecular sciences · 2024Review
- D-2-hydroxyglutarate supports a tolerogenic phenotype with lowered major histocompatibility class II expression in non-malignant dendritic cells and acute myeloid leukemia cells.Haematologica · 2024Article
- Targeting glycolysis to rescue 2-hydroxyglutarate immunosuppressive effects in dendritic cells and acute myeloid leukemia.Haematologica · 2024Article
24 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
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
D-2-hydroxyglutarate (D-2HG) is released by various types of malignant cells including acute myeloid leukemia (AML) blasts carrying isocitrate dehydrogenase (IDH) gain-of-function mutations. D-2HG acting as an oncometabolite promotes proliferation, anoikis, and differentiation block of hematopoietic cells in an autocrine fashion. However, prognostic impact of IDH mutations and high D-2HG levels remains controversial and might depend on the overall mutational context. An increasing number of studies focus on the permissive environment created by AML blasts to promote immune evasion. Impact of D-2HG on immune cells remains incompletely understood. Here, we sought out to investigate the effects of D-2HG on T-cells as key mediators of anti-AML immunity. D-2HG was efficiently taken up by T-cells in vitro, which is in line with high 2-HG levels measured in T-cells isolated from AML patients carrying IDH mutations. T-cell activation was slightly impacted by D-2HG. However, D-2HG triggered HIF-1a protein destabilization resulting in metabolic skewing towards oxidative phosphorylation, increased regulatory T-cell (Treg) frequency, and reduced T helper 17 (Th17) polarization. Our data suggest for the first time that D-2HG might contribute to fine tuning of immune responses.
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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.