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; Hanggi, Daniel; Dorsch, Marion; Suvà, Mario L; Niemeyer, Barbara A; von Deimling, Andreas; Wick, Wolfgang; Platten, Michael     «

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, Jessi...     »

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.     «

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 calci...     »