TY  - JOUR
AU  - Bunse, Lukas
AU  - Pusch, Stefan
AU  - Bunse, Theresa
AU  - Sahm, Felix
AU  - Sanghvi, Khwab
AU  - Friedrich, Mirco
AU  - Alansary, Dalia
AU  - Sonner, Jana
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 Sophie
AU  - Marsh, Kelly
AU  - Steadman, Mya
AU  - Zhu, Dongwei
AU  - Nicolay, Brandon
AU  - Wiestler, Benedikt
AU  - Breckwoldt, Michael
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
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
TI  - Suppression of antitumor T cell immunity by the oncometabolite (R)-2-hydroxyglutarate.
JO  - Nature medicine
VL  - 24
IS  - 8
SN  - 1546-170X
CY  - New York, NY
PB  - Nature America Inc.
M1  - DKFZ-2018-01287
SP  - 1192 - 1203
PY  - 2018
N1  - #DKFZ-MOST-GR-2526#
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.
LB  - PUB:(DE-HGF)16
C6  - pmid:29988124
DO  - DOI:10.1038/s41591-018-0095-6
UR  - https://inrepo02.dkfz.de/record/136849
ER  -