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| 024 | 7 | _ | |a pmid:35121943 |2 pmid |
| 024 | 7 | _ | |a 10.1038/s43018-021-00201-z |2 doi |
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| 037 | _ | _ | |a DZNE-2021-00742 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a Friedrich, Mirco |b 0 |
| 245 | _ | _ | |a Tryptophan metabolism drives dynamic immunosuppressive myeloid states in IDH-mutant gliomas |
| 260 | _ | _ | |a London |c 2021 |b Nature Research |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1683881213_24932 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
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| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a The dynamics and phenotypes of intratumoral myeloid cells during tumor progression are poorly understood. Here we define myeloid cellular states in gliomas by longitudinal single-cell profiling and demonstrate their strict control by the tumor genotype: in isocitrate dehydrogenase (IDH)-mutant tumors, differentiation of infiltrating myeloid cells is blocked, resulting in an immature phenotype. In late-stage gliomas, monocyte-derived macrophages drive tolerogenic alignment of the microenvironment, thus preventing T cell response. We define the IDH-dependent tumor education of infiltrating macrophages to be causally related to a complex re-orchestration of tryptophan metabolism, resulting in activation of the aryl hydrocarbon receptor. We further show that the altered metabolism of IDH-mutant gliomas maintains this axis in bystander cells and that pharmacological inhibition of tryptophan metabolism can reverse immunosuppression. In conclusion, we provide evidence of a glioma genotype-dependent intratumoral network of resident and recruited myeloid cells and identify tryptophan metabolism as a target for immunotherapy of IDH-mutant tumors. |
| 536 | _ | _ | |a 353 - Clinical and Health Care Research (POF4-353) |0 G:(DE-HGF)POF4-353 |c POF4-353 |f POF IV |x 0 |
| 588 | _ | _ | |a Dataset connected to CrossRef, Journals: pub.dzne.de |
| 650 | _ | 7 | |a Tryptophan |0 8DUH1N11BX |2 NLM Chemicals |
| 650 | _ | 7 | |a Isocitrate Dehydrogenase |0 EC 1.1.1.41 |2 NLM Chemicals |
| 650 | _ | 2 | |a Brain Neoplasms: genetics |2 MeSH |
| 650 | _ | 2 | |a Glioma: genetics |2 MeSH |
| 650 | _ | 2 | |a Humans |2 MeSH |
| 650 | _ | 2 | |a Immunotherapy |2 MeSH |
| 650 | _ | 2 | |a Isocitrate Dehydrogenase: genetics |2 MeSH |
| 650 | _ | 2 | |a Tryptophan: therapeutic use |2 MeSH |
| 650 | _ | 2 | |a Tumor Microenvironment: genetics |2 MeSH |
| 700 | 1 | _ | |a Sankowski, Roman |0 0000-0001-9215-8021 |b 1 |
| 700 | 1 | _ | |a Bunse, Lukas |0 0000-0002-4490-7574 |b 2 |
| 700 | 1 | _ | |a Kilian, Michael |b 3 |
| 700 | 1 | _ | |a Green, Edward |b 4 |
| 700 | 1 | _ | |a Ramallo Guevara, Carina |b 5 |
| 700 | 1 | _ | |a Pusch, Stefan |0 0000-0002-3407-4249 |b 6 |
| 700 | 1 | _ | |a Poschet, Gernot |b 7 |
| 700 | 1 | _ | |a Sanghvi, Khwab |b 8 |
| 700 | 1 | _ | |a Hahn, Markus |b 9 |
| 700 | 1 | _ | |a Bunse, Theresa |0 0000-0003-1834-4269 |b 10 |
| 700 | 1 | _ | |a Münch, Philipp |b 11 |
| 700 | 1 | _ | |a Gegner, Hagen M. |b 12 |
| 700 | 1 | _ | |a Sonner, Jana K. |0 0000-0002-4700-272X |b 13 |
| 700 | 1 | _ | |a von Landenberg, Anna |b 14 |
| 700 | 1 | _ | |a Cichon, Frederik |b 15 |
| 700 | 1 | _ | |a Aslan, Katrin |b 16 |
| 700 | 1 | _ | |a Trobisch, Tim |b 17 |
| 700 | 1 | _ | |a Schirmer, Lucas |0 0000-0001-7142-4116 |b 18 |
| 700 | 1 | _ | |a Abu-Sammour, Denis |b 19 |
| 700 | 1 | _ | |a Kessler, Tobias |b 20 |
| 700 | 1 | _ | |a Ratliff, Miriam |b 21 |
| 700 | 1 | _ | |a Schrimpf, Daniel |b 22 |
| 700 | 1 | _ | |a Sahm, Felix |0 0000-0001-5441-1962 |b 23 |
| 700 | 1 | _ | |a Hopf, Carsten |0 0000-0003-0802-6451 |b 24 |
| 700 | 1 | _ | |a Heiland, Dieter H. |0 0000-0002-9258-3033 |b 25 |
| 700 | 1 | _ | |a Schnell, Oliver |b 26 |
| 700 | 1 | _ | |a Beck, Jürgen |b 27 |
| 700 | 1 | _ | |a Böttcher, Chotima |0 P:(DE-2719)9000034 |b 28 |u dzne |
| 700 | 1 | _ | |a Fernandez-Zapata, Camila |0 0000-0003-4795-6053 |b 29 |
| 700 | 1 | _ | |a Priller, Josef |0 P:(DE-2719)2811122 |b 30 |u dzne |
| 700 | 1 | _ | |a Heiland, Sabine |b 31 |
| 700 | 1 | _ | |a Gutcher, Ilona |b 32 |
| 700 | 1 | _ | |a Quintana, Francisco J. |b 33 |
| 700 | 1 | _ | |a von Deimling, Andreas |0 0000-0002-5863-540X |b 34 |
| 700 | 1 | _ | |a Wick, Wolfgang |0 0000-0002-6171-634X |b 35 |
| 700 | 1 | _ | |a Prinz, Marco |0 0000-0002-0349-1955 |b 36 |
| 700 | 1 | _ | |a Platten, Michael |0 0000-0002-4746-887X |b 37 |e Corresponding author |
| 773 | _ | _ | |a 10.1038/s43018-021-00201-z |g Vol. 2, no. 7, p. 723 - 740 |0 PERI:(DE-600)3005299-3 |n 7 |p 723 - 740 |t Nature cancer |v 2 |y 2021 |x 2662-1347 |
| 856 | 4 | _ | |u https://www.nature.com/articles/s43018-021-00201-z |
| 856 | 4 | _ | |u https://pub.dzne.de/record/155564/files/19580.pdf |y OpenAccess |
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