ArticleNature medicine2018
Suppression of antitumor T cell immunity by the oncometabolite (R)-2-hydroxyglutarate.
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Article in Nature medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 383 papers, 1 of them a synthesis that pooled it.
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383citing papers in PubMed, 1 pooled it
26.5field-weighted citation impact, top 1% of its field
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Who cites it
383 citing papers in PubMed, 1 synthesis or guideline pooled it, 519 citations in OpenAlex.
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- Cholangiocarcinoma:Unveiling the cold tumor microenvironment and strategies for immune rejuvenation.Oncogene · 2026Review
- Alterations in 3D-DNA architecture drive unique leukemic profiles in IDH1- and DNMT3A-mutant acute myeloid leukemia.Leukemia · 2026Article
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- Circulating tumor DNA-based detection of molecular residual disease in isocitrate dehydrogenase-mutant cholangiocarcinoma for biomarker-guided therapy.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Brain barriers at the crossroads of glioma immune surveillance and immunotherapy response.Nature reviews. Cancer · 2026Review
- IDH-Mutant Diffuse Glioma: From Metabolic Origins to Targeted Therapy.Journal of clinical medicine · 2026Review
- Metabolic Bottlenecks and Opportunities: Reshaping the Tumor Microenvironment for Cancer Immunotherapy.Cells · 2026Review
- IDH1-mutant vaccine in newly diagnosed astrocytoma: final analysis of the multicenter, single-arm, open-label, first-in-human phase 1 NOA16 trial.Nature cancer · 2026Article
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- Regulation of immune checkpoint molecules in cancer immune evasion and therapy.Nature reviews. Cancer · 2026Review
- OT-55 reshapes tolerogenic BH3-mimetic-induced apoptosis toward immunogenic cell death in acute myeloid leukemia, potentiating PD-1/Tim-3 blockade.Cell death & disease · 2026Article
- Metabolites as signalling molecules in the tumour immune microenvironment.Nature reviews. Immunology · 2026Review
- The vascular niche: an orchestrator of the spatiotemporal dynamics of distant metastasis.Acta pharmacologica Sinica · 2026Review
- Solute carrier transporters as metabolic gatekeepers in tumor-microenvironment crosstalk.Acta pharmacologica Sinica · 2026Review
- Redefining Liver Transplantation Indications for Hepatic Malignancies in the Era of Precision Transplant Oncology: An Up-to-Date Narrative Review.Journal of clinical medicine · 2026Review
- Current and emerging therapies in IDH-mutant glioma.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
323 more citing papers are in PubMed but not listed here.
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Authors and funding
56 authors at 13 institutions in 4 countries.
Lukas BunseGerman Cancer Consortium (DKTK) Clinical Cooperation Unit (CCU) Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.ORCID http://orcid.org/0000-0002-4490-7574
Stefan PuschDepartment of Neuropathology, Heidelberg University Medical Center, Heidelberg, Germany.ORCID http://orcid.org/0000-0002-3407-4249
Theresa BunseGerman Cancer Consortium (DKTK) Clinical Cooperation Unit (CCU) Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Felix SahmDepartment of Neuropathology, Heidelberg University Medical Center, Heidelberg, Germany.
Khwab SanghviGerman Cancer Consortium (DKTK) Clinical Cooperation Unit (CCU) Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Mirco FriedrichGerman Cancer Consortium (DKTK) Clinical Cooperation Unit (CCU) Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Dalia AlansaryMolecular Biophysics, Center for Integrative Physiology and Molecular Medicine, School of Medicine, Saarland University, Homburg, Germany.
Jana K SonnerGerman Cancer Consortium (DKTK) Clinical Cooperation Unit (CCU) Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Edward GreenGerman Cancer Consortium (DKTK) Clinical Cooperation Unit (CCU) Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Katrin DeumelandtGerman Cancer Consortium (DKTK) Clinical Cooperation Unit (CCU) Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Michael KilianGerman Cancer Consortium (DKTK) Clinical Cooperation Unit (CCU) Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Cyril NeftelBroad Institute of Harvard and MIT and Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Stefanie UhligFlowCore Mannheim and Institute of Transfusion Medicine and Immunology, Mannheim, Germany.
Tobias KesslerDepartment of Neurology, Heidelberg University Medical Center, Heidelberg, Germany.
Anna von LandenbergGerman Cancer Consortium (DKTK) Clinical Cooperation Unit (CCU) Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Anna S BerghoffDKTK CCU Neurooncology, DKFZ, Heidelberg, Germany.
Kelly MarshAgios Pharmaceuticals, Inc., Cambridge, MA, USA.
Mya SteadmanAgios Pharmaceuticals, Inc., Cambridge, MA, USA.
Dongwei ZhuAgios Pharmaceuticals, Inc., Cambridge, MA, USA.
Brandon NicolayAgios Pharmaceuticals, Inc., Cambridge, MA, USA.
Benedikt WiestlerDepartment of Diagnostic and Interventional Neuroradiology, Neuro-Kopf-Zentrum, Klinikum rechts der Isar, Technical University Munich, Munich, Germany.
Michael O BreckwoldtGerman Cancer Consortium (DKTK) Clinical Cooperation Unit (CCU) Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Ruslan Al-AliMax Eder Junior Group on Low Grade Gliomas, Heidelberg University Medical Center, Heidelberg, Germany.
Simone Karcher-BauschGerman Cancer Consortium (DKTK) Clinical Cooperation Unit (CCU) Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Matthias BozzaDNA Vectors Unit, DKFZ, Heidelberg, Germany.
Iris OezenGerman Cancer Consortium (DKTK) Clinical Cooperation Unit (CCU) Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Magdalena KramerGerman Cancer Consortium (DKTK) Clinical Cooperation Unit (CCU) Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Jochen MeyerDepartment of Neuropathology, Heidelberg University Medical Center, Heidelberg, Germany.
Antje HabelDepartment of Neuropathology, Heidelberg University Medical Center, Heidelberg, Germany.
Jessica EiselDepartment of Neuropathology, Heidelberg University Medical Center, Heidelberg, Germany.
Gernot PoschetCenter for Organismal Studies, University Heidelberg, Heidelberg, Germany.
Michael WellerDepartment of Neurology, University Hospital and University of Zurich, Zurich, Switzerland.
Matthias PreusserCNS Tumors Unit, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
Minou Nadji-OhlDepartment of Neurosurgery, Stuttgart Clinics, Stuttgart, Germany.
Niklas ThonDepartment of Neurosurgery, Klinikum Grosshadern, Ludwig-Maximilians-University, Munich, Germany.
Michael C BurgerDr. Senckenberg Institute of Neurooncology, Goethe University Hospital, Frankfurt, Germany.
Patrick N HarterDKTK Partner Site Frankfurt/Mainz, Frankfurt, Germany.
Miriam RatliffDKTK CCU Neurooncology, DKFZ, Heidelberg, Germany.
Richard HarbottleDNA Vectors Unit, DKFZ, Heidelberg, Germany.
Axel BennerDivision of Biostatistics, DKFZ, Heidelberg, Germany.
Daniel SchrimpfDepartment of Neuropathology, Heidelberg University Medical Center, Heidelberg, Germany.
Jürgen OkunMetabolic Center Heidelberg, University Children's Hospital, Heidelberg, Germany.
Christel Herold-MendeDivision of Experimental Neurosurgery, Department of Neurosurgery, Heidelberg University Medical Center, Heidelberg, Germany.
Sevin TurcanMax Eder Junior Group on Low Grade Gliomas, Heidelberg University Medical Center, Heidelberg, Germany.
Stefan KaulfussResearch and Development, Pharmaceuticals, Bayer AG, Berlin, Germany.
Holger Hess-StumppResearch and Development, Pharmaceuticals, Bayer AG, Berlin, Germany.
Karen BiebackFlowCore Mannheim and Institute of Transfusion Medicine and Immunology, Mannheim, Germany.
Daniel P CahillDepartment of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Karl H PlateDKTK Partner Site Frankfurt/Mainz, Frankfurt, Germany.
Daniel HänggiNeurosurgery Clinic, University Hospital Mannheim, Mannheim, Germany.
Marion DorschAgios Pharmaceuticals, Inc., Cambridge, MA, USA.
Mario L SuvàBroad Institute of Harvard and MIT and Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-9898-5351
Barbara A NiemeyerMolecular Biophysics, Center for Integrative Physiology and Molecular Medicine, School of Medicine, Saarland University, Homburg, Germany.
Andreas von DeimlingFaculty of Biosciences, Heidelberg University, Heidelberg, Germany.
Wolfgang WickDepartment of Neurology, Heidelberg University Medical Center, Heidelberg, Germany.ORCID http://orcid.org/0000-0002-6171-634X
Michael PlattenGerman Cancer Consortium (DKTK) Clinical Cooperation Unit (CCU) Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany. m.platten@dkfz.de.
Heidelberg University · DEGerman Cancer Research Center · DEAgios Pharmaceuticals (United States) · USGoethe University Frankfurt · DEBayer (Germany) · DEBroad Institute · USSaarland University · DEUniversity of Mannheim · DEComprehensive Cancer Center Vienna · ATHarvard University · USLudwig-Maximilians-Universität München · DETUM Klinikum · DEUniversity of Zurich · CH
Funding
No grant is acknowledged in the PubMed record.
Abstract
The oncometabolite (R)-2-hydroxyglutarate (R-2-HG) produced by isocitrate dehydrogenase (IDH) mutations promotes gliomagenesis via DNA and histone methylation. Here, we identify an additional activity of R-2-HG: tumor cell-derived R-2-HG is taken up by T cells where it induces a perturbation of nuclear factor of activated T cells transcriptional activity and polyamine biosynthesis, resulting in suppression of T cell activity. IDH1-mutant gliomas display reduced T cell abundance and altered calcium signaling. Antitumor immunity to experimental syngeneic IDH1-mutant tumors induced by IDH1-specific vaccine or checkpoint inhibition is improved by inhibition of the neomorphic enzymatic function of mutant IDH1. These data attribute a novel, non-tumor cell-autonomous role to an oncometabolite in shaping the tumor immune microenvironment.
Indexed as
ImmunityAdenosine TriphosphateAnimalsApoptosisBrain NeoplasmsCalciumCell Line, TumorCell ProliferationGliomaGlutaratesHumansIsocitrate DehydrogenaseLymphocyte ActivationMice, Inbred C57BLMutationNFATC Transcription FactorsAdenosine Triphosphatealpha-hydroxyglutarateCalciumGlutaratesIDH1 protein, humanIsocitrate DehydrogenaseNFATC Transcription FactorsPolyaminesReceptors, Antigen, T-CellRNA, Messenger
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