| Title |
Suppression of antitumor T cell immunity by the oncometabolite (R)-2-hydroxyglutarate
|
|---|---|
| Published in |
Nature Medicine, July 2018
|
| DOI | 10.1038/s41591-018-0095-6 |
| Pubmed ID | |
| Authors |
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, Marion Dorsch, Mario L. Suvà, Barbara A. Niemeyer, Andreas von Deimling, Wolfgang Wick, Michael Platten |
| 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. |
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X Demographics
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 7 | 28% |
| Japan | 2 | 8% |
| United Kingdom | 2 | 8% |
| Belgium | 1 | 4% |
| Italy | 1 | 4% |
| France | 1 | 4% |
| Iraq | 1 | 4% |
| Portugal | 1 | 4% |
| Germany | 1 | 4% |
| Other | 0 | 0% |
| Unknown | 8 | 32% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 15 | 60% |
| Scientists | 9 | 36% |
| Science communicators (journalists, bloggers, editors) | 1 | 4% |
Mendeley demographics
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 390 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 64 | 16% |
| Researcher | 50 | 13% |
| Student > Master | 35 | 9% |
| Student > Bachelor | 33 | 8% |
| Student > Doctoral Student | 24 | 6% |
| Other | 59 | 15% |
| Unknown | 125 | 32% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 86 | 22% |
| Medicine and Dentistry | 51 | 13% |
| Immunology and Microbiology | 34 | 9% |
| Agricultural and Biological Sciences | 21 | 5% |
| Neuroscience | 14 | 4% |
| Other | 48 | 12% |
| Unknown | 136 | 35% |