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

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Suppression of antitumor T cell immunity by the oncometabolite (R)-2-hydroxyglutarate. / Bunse, Lukas; Pusch, Stefan; Bunse, Theresa; Sahm, Felix; Sanghvi, Khwab; Friedrich, Mirco; Alansary, Dalia; Sonner, Jana K; Green, Edward; Deumelandt, Katrin; Kilian, Michael; Neftel, Cyril; Uhlig, Stefanie; Kessler, Tobias; von Landenberg, Anna; Berghoff, Anna S; Marsh, Kelly; Steadman, Mya; Zhu, Dongwei; Nicolay, Brandon; Wiestler, Benedikt; Breckwoldt, Michael O; Al-Ali, Ruslan; Karcher-Bausch, Simone; Bozza, Matthias; Oezen, Iris; Kramer, Magdalena; Meyer, Jochen; Habel, Antje; Eisel, Jessica; Poschet, Gernot; Weller, Michael; Preusser, Matthias; Nadji-Ohl, Minou; Thon, Niklas; Burger, Michael C; Harter, Patrick N; Ratliff, Miriam; Harbottle, Richard; Benner, Axel; Schrimpf, Daniel; Okun, Jürgen; Herold-Mende, Christel; Turcan, Sevin; Kaulfuss, Stefan; Hess-Stumpp, Holger; Bieback, Karen; Cahill, Daniel P; Plate, Karl H; Hänggi, Daniel; Dorsch, Marion; Suvà, Mario L; Niemeyer, Barbara A; von Deimling, Andreas; Wick, Wolfgang; Platten, Michael.

In: NAT MED, Vol. 24, No. 8, 08.2018, p. 1192-1203.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Bunse, L, Pusch, S, Bunse, T, Sahm, F, Sanghvi, K, Friedrich, M, Alansary, D, Sonner, JK, Green, E, Deumelandt, K, Kilian, M, Neftel, C, Uhlig, S, Kessler, T, von Landenberg, A, Berghoff, AS, Marsh, K, Steadman, M, Zhu, D, Nicolay, B, Wiestler, B, Breckwoldt, MO, Al-Ali, R, Karcher-Bausch, S, Bozza, M, Oezen, I, Kramer, M, Meyer, J, Habel, A, Eisel, J, Poschet, G, Weller, M, Preusser, M, Nadji-Ohl, M, Thon, N, Burger, MC, Harter, PN, Ratliff, M, Harbottle, R, Benner, A, Schrimpf, D, Okun, J, Herold-Mende, C, Turcan, S, Kaulfuss, S, Hess-Stumpp, H, Bieback, K, Cahill, DP, Plate, KH, Hänggi, D, Dorsch, M, Suvà, ML, Niemeyer, BA, von Deimling, A, Wick, W & Platten, M 2018, 'Suppression of antitumor T cell immunity by the oncometabolite (R)-2-hydroxyglutarate', NAT MED, vol. 24, no. 8, pp. 1192-1203. https://doi.org/10.1038/s41591-018-0095-6

APA

Bunse, L., Pusch, S., Bunse, T., Sahm, F., Sanghvi, K., Friedrich, M., Alansary, D., Sonner, J. K., Green, E., Deumelandt, K., Kilian, M., Neftel, C., Uhlig, S., Kessler, T., von Landenberg, A., Berghoff, A. S., Marsh, K., Steadman, M., Zhu, D., ... Platten, M. (2018). Suppression of antitumor T cell immunity by the oncometabolite (R)-2-hydroxyglutarate. NAT MED, 24(8), 1192-1203. https://doi.org/10.1038/s41591-018-0095-6

Vancouver

Bunse L, Pusch S, Bunse T, Sahm F, Sanghvi K, Friedrich M et al. Suppression of antitumor T cell immunity by the oncometabolite (R)-2-hydroxyglutarate. NAT MED. 2018 Aug;24(8):1192-1203. https://doi.org/10.1038/s41591-018-0095-6

Bibtex

@article{e989c2cd9050408c8ed2c85611aada0f,
title = "Suppression of antitumor T cell immunity by the oncometabolite (R)-2-hydroxyglutarate",
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.",
keywords = "Adenosine Triphosphate/metabolism, Animals, Apoptosis, Brain Neoplasms/genetics, Calcium/metabolism, Cell Line, Tumor, Cell Proliferation, Glioma/genetics, Glutarates/metabolism, Humans, Immunity, Isocitrate Dehydrogenase/genetics, Lymphocyte Activation/immunology, Mice, Inbred C57BL, Mutation/genetics, NFATC Transcription Factors/metabolism, Paracrine Communication, Polyamines/metabolism, RNA, Messenger/genetics, Receptors, Antigen, T-Cell/metabolism, Signal Transduction, T-Lymphocytes/immunology",
author = "Lukas Bunse and Stefan Pusch and Theresa Bunse and Felix Sahm and Khwab Sanghvi and Mirco Friedrich and Dalia Alansary and Sonner, {Jana K} and Edward Green and Katrin Deumelandt and Michael Kilian and Cyril Neftel and Stefanie Uhlig and Tobias Kessler and {von Landenberg}, Anna and Berghoff, {Anna S} and Kelly Marsh and Mya Steadman and Dongwei Zhu and Brandon Nicolay and Benedikt Wiestler and Breckwoldt, {Michael O} and Ruslan Al-Ali and Simone Karcher-Bausch and Matthias Bozza and Iris Oezen and Magdalena Kramer and Jochen Meyer and Antje Habel and Jessica Eisel and Gernot Poschet and Michael Weller and Matthias Preusser and Minou Nadji-Ohl and Niklas Thon and Burger, {Michael C} and Harter, {Patrick N} and Miriam Ratliff and Richard Harbottle and Axel Benner and Daniel Schrimpf and J{\"u}rgen Okun and Christel Herold-Mende and Sevin Turcan and Stefan Kaulfuss and Holger Hess-Stumpp and Karen Bieback and Cahill, {Daniel P} and Plate, {Karl H} and Daniel H{\"a}nggi and Marion Dorsch and Suv{\`a}, {Mario L} and Niemeyer, {Barbara A} and {von Deimling}, Andreas and Wolfgang Wick and Michael Platten",
year = "2018",
month = aug,
doi = "10.1038/s41591-018-0095-6",
language = "English",
volume = "24",
pages = "1192--1203",
journal = "NAT MED",
issn = "1078-8956",
publisher = "NATURE PUBLISHING GROUP",
number = "8",

}

RIS

TY - JOUR

T1 - Suppression of antitumor T cell immunity by the oncometabolite (R)-2-hydroxyglutarate

AU - Bunse, Lukas

AU - Pusch, Stefan

AU - Bunse, Theresa

AU - Sahm, Felix

AU - Sanghvi, Khwab

AU - Friedrich, Mirco

AU - Alansary, Dalia

AU - Sonner, Jana K

AU - Green, Edward

AU - Deumelandt, Katrin

AU - Kilian, Michael

AU - Neftel, Cyril

AU - Uhlig, Stefanie

AU - Kessler, Tobias

AU - von Landenberg, Anna

AU - Berghoff, Anna S

AU - Marsh, Kelly

AU - Steadman, Mya

AU - Zhu, Dongwei

AU - Nicolay, Brandon

AU - Wiestler, Benedikt

AU - Breckwoldt, Michael O

AU - Al-Ali, Ruslan

AU - Karcher-Bausch, Simone

AU - Bozza, Matthias

AU - Oezen, Iris

AU - Kramer, Magdalena

AU - Meyer, Jochen

AU - Habel, Antje

AU - Eisel, Jessica

AU - Poschet, Gernot

AU - Weller, Michael

AU - Preusser, Matthias

AU - Nadji-Ohl, Minou

AU - Thon, Niklas

AU - Burger, Michael C

AU - Harter, Patrick N

AU - Ratliff, Miriam

AU - Harbottle, Richard

AU - Benner, Axel

AU - Schrimpf, Daniel

AU - Okun, Jürgen

AU - Herold-Mende, Christel

AU - Turcan, Sevin

AU - Kaulfuss, Stefan

AU - Hess-Stumpp, Holger

AU - Bieback, Karen

AU - Cahill, Daniel P

AU - Plate, Karl H

AU - Hänggi, Daniel

AU - Dorsch, Marion

AU - Suvà, Mario L

AU - Niemeyer, Barbara A

AU - von Deimling, Andreas

AU - Wick, Wolfgang

AU - Platten, Michael

PY - 2018/8

Y1 - 2018/8

N2 - 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.

AB - 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.

KW - Adenosine Triphosphate/metabolism

KW - Animals

KW - Apoptosis

KW - Brain Neoplasms/genetics

KW - Calcium/metabolism

KW - Cell Line, Tumor

KW - Cell Proliferation

KW - Glioma/genetics

KW - Glutarates/metabolism

KW - Humans

KW - Immunity

KW - Isocitrate Dehydrogenase/genetics

KW - Lymphocyte Activation/immunology

KW - Mice, Inbred C57BL

KW - Mutation/genetics

KW - NFATC Transcription Factors/metabolism

KW - Paracrine Communication

KW - Polyamines/metabolism

KW - RNA, Messenger/genetics

KW - Receptors, Antigen, T-Cell/metabolism

KW - Signal Transduction

KW - T-Lymphocytes/immunology

U2 - 10.1038/s41591-018-0095-6

DO - 10.1038/s41591-018-0095-6

M3 - SCORING: Journal article

C2 - 29988124

VL - 24

SP - 1192

EP - 1203

JO - NAT MED

JF - NAT MED

SN - 1078-8956

IS - 8

ER -