| Literature DB >> 29988124 |
Lukas Bunse1,2,3,4, Stefan Pusch5,6, Theresa Bunse1,3,7, Felix Sahm5,6, Khwab Sanghvi1,4, Mirco Friedrich1, Dalia Alansary8, Jana K Sonner1, Edward Green1, Katrin Deumelandt1,4, Michael Kilian1,4, Cyril Neftel9, Stefanie Uhlig10, Tobias Kessler2,3,11, Anna von Landenberg1, Anna S Berghoff11,12,13, Kelly Marsh14, Mya Steadman14, Dongwei Zhu14, Brandon Nicolay14, Benedikt Wiestler15, Michael O Breckwoldt1,16, Ruslan Al-Ali17, Simone Karcher-Bausch1, Matthias Bozza18, Iris Oezen1, Magdalena Kramer1, Jochen Meyer5,6, Antje Habel5,6, Jessica Eisel5,6, Gernot Poschet19, Michael Weller20, Matthias Preusser13,21, Minou Nadji-Ohl22, Niklas Thon23, Michael C Burger24,25, Patrick N Harter25,26, Miriam Ratliff11,27, Richard Harbottle18, Axel Benner28, Daniel Schrimpf5,6, Jürgen Okun29, Christel Herold-Mende30, Sevin Turcan17, Stefan Kaulfuss31, Holger Hess-Stumpp31, Karen Bieback10, Daniel P Cahill32, Karl H Plate25,26, Daniel Hänggi27, Marion Dorsch14, Mario L Suvà9, Barbara A Niemeyer8, Andreas von Deimling4,5, Wolfgang Wick2,3,11, Michael Platten33,34,35,36.
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.Entities:
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Year: 2018 PMID： 29988124 DOI： 10.1038/s41591-018-0095-6
Source DB: PubMed Journal: Nat Med ISSN： 1078-8956 Impact factor: 53.440