Suppression of antitumor T cell immunity by the oncometabolite (R)-2-hydroxyglutarate

被引：0

作者：

Lukas Bunse

Stefan Pusch

Theresa Bunse

Felix Sahm

Khwab Sanghvi

Mirco Friedrich

Dalia Alansary

Jana K. Sonner

Edward Green

Katrin Deumelandt

Michael Kilian

Cyril Neftel

Stefanie Uhlig

Tobias Kessler

Anna von Landenberg

Anna S. Berghoff

Kelly Marsh

Mya Steadman

Dongwei Zhu

Brandon Nicolay

Benedikt Wiestler

Michael O. Breckwoldt

Ruslan Al-Ali

Simone Karcher-Bausch

Matthias Bozza

Iris Oezen

Magdalena Kramer

Jochen Meyer

Antje Habel

Jessica Eisel

Gernot Poschet

Michael Weller

Matthias Preusser

Minou Nadji-Ohl

Niklas Thon

Michael C. Burger

Patrick N. Harter

Miriam Ratliff

Richard Harbottle

Axel Benner

Daniel Schrimpf

Jürgen Okun

Christel Herold-Mende

Sevin Turcan

Stefan Kaulfuss

Holger Hess‐Stumpp

Karen Bieback

Daniel P. Cahill

Karl H. Plate

Daniel Hänggi

机构：

[1] German Cancer Research Center (DKFZ),German Cancer Consortium (DKTK) Clinical Cooperation Unit (CCU) Neuroimmunology and Brain Tumor Immunology

[2] Heidelberg University Medical Center,Department of Neurology

[3] National Center for Tumor Diseases Heidelberg,Faculty of Biosciences

[4] DKTK,Department of Neuropathology

[5] Heidelberg University,Department of Neurology

[6] Heidelberg University Medical Center,Molecular Biophysics, Center for Integrative Physiology and Molecular Medicine, School of Medicine

[7] DKTK CCU Neuropathology,Broad Institute of Harvard and MIT and Department of Pathology and Center for Cancer Research

[8] DKFZ,Institute of Neurology

[9] University Hospital and Medical Faculty Mannheim,CNS Tumors Unit, Comprehensive Cancer Center

[10] Saarland University,Department of Diagnostic and Interventional Neuroradiology, Neuro

[11] Massachusetts General Hospital and Harvard Medical School,Kopf

[12] FlowCore Mannheim and Institute of Transfusion Medicine and Immunology,Zentrum, Klinikum rechts der Isar

[13] DKTK CCU Neurooncology,Department of Neuroradiology

[14] DKFZ,Center for Organismal Studies

[15] Medical University of Vienna,Department of Neurology

[16] Medical University of Vienna,Department for Medicine I, Clinical Division of Oncology

[17] Agios Pharmaceuticals,Department of Neurosurgery

[18] Inc.,Department of Neurosurgery, Klinikum Grosshadern

[19] Technical University Munich,Dr. Senckenberg Institute of Neurooncology

[20] Heidelberg University Medical Center,Institute of Neurology (Edinger Institute)

[21] Max Eder Junior Group on Low Grade Gliomas,Neurosurgery Clinic

[22] Heidelberg University Medical Center,Metabolic Center Heidelberg

[23] DNA Vectors Unit,Division of Experimental Neurosurgery, Department of Neurosurgery

[24] DKFZ,Research and Development, Pharmaceuticals

[25] University Heidelberg,Department of Neurosurgery

[26] University Hospital and University of Zurich,undefined

[27] Medical University of Vienna,undefined

[28] Stuttgart Clinics,undefined

[29] Ludwig-Maximilians-University,undefined

[30] Goethe University Hospital,undefined

[31] DKTK Partner Site Frankfurt/Mainz,undefined

[32] University Hospital and Medical Faculty,undefined

[33] Goethe University,undefined

[34] University Hospital Mannheim,undefined

[35] Division of Biostatistics,undefined

[36] DKFZ,undefined

[37] University Children’s Hospital,undefined

[38] Heidelberg University Medical Center,undefined

[39] Bayer AG,undefined

[40] Massachusetts General Hospital,undefined

[41] Harvard Medical School,undefined

来源：

Nature Medicine | 2018年 / 24卷

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摘要：

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.

引用

页码：1192 / 1203

页数：11

共 50 条

[1] Suppression of antitumor T cell immunity by the oncometabolite (R)-2-hydroxyglutarate
Bunse, Lukas
Pusch, Stefan
Bunse, Theresa
Sahm, Felix
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