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000155564 1001_ $$aFriedrich, Mirco$$b0
000155564 245__ $$aTryptophan metabolism drives dynamic immunosuppressive myeloid states in IDH-mutant gliomas
000155564 260__ $$aLondon$$bNature Research$$c2021
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000155564 520__ $$aThe dynamics and phenotypes of intratumoral myeloid cells during tumor progression are poorly understood. Here we define myeloid cellular states in gliomas by longitudinal single-cell profiling and demonstrate their strict control by the tumor genotype: in isocitrate dehydrogenase (IDH)-mutant tumors, differentiation of infiltrating myeloid cells is blocked, resulting in an immature phenotype. In late-stage gliomas, monocyte-derived macrophages drive tolerogenic alignment of the microenvironment, thus preventing T cell response. We define the IDH-dependent tumor education of infiltrating macrophages to be causally related to a complex re-orchestration of tryptophan metabolism, resulting in activation of the aryl hydrocarbon receptor. We further show that the altered metabolism of IDH-mutant gliomas maintains this axis in bystander cells and that pharmacological inhibition of tryptophan metabolism can reverse immunosuppression. In conclusion, we provide evidence of a glioma genotype-dependent intratumoral network of resident and recruited myeloid cells and identify tryptophan metabolism as a target for immunotherapy of IDH-mutant tumors.
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000155564 650_7 $$08DUH1N11BX$$2NLM Chemicals$$aTryptophan
000155564 650_7 $$0EC 1.1.1.41$$2NLM Chemicals$$aIsocitrate Dehydrogenase
000155564 650_2 $$2MeSH$$aBrain Neoplasms: genetics
000155564 650_2 $$2MeSH$$aGlioma: genetics
000155564 650_2 $$2MeSH$$aHumans
000155564 650_2 $$2MeSH$$aImmunotherapy
000155564 650_2 $$2MeSH$$aIsocitrate Dehydrogenase: genetics
000155564 650_2 $$2MeSH$$aTryptophan: therapeutic use
000155564 650_2 $$2MeSH$$aTumor Microenvironment: genetics
000155564 7001_ $$00000-0001-9215-8021$$aSankowski, Roman$$b1
000155564 7001_ $$00000-0002-4490-7574$$aBunse, Lukas$$b2
000155564 7001_ $$aKilian, Michael$$b3
000155564 7001_ $$aGreen, Edward$$b4
000155564 7001_ $$aRamallo Guevara, Carina$$b5
000155564 7001_ $$00000-0002-3407-4249$$aPusch, Stefan$$b6
000155564 7001_ $$aPoschet, Gernot$$b7
000155564 7001_ $$aSanghvi, Khwab$$b8
000155564 7001_ $$aHahn, Markus$$b9
000155564 7001_ $$00000-0003-1834-4269$$aBunse, Theresa$$b10
000155564 7001_ $$aMünch, Philipp$$b11
000155564 7001_ $$aGegner, Hagen M.$$b12
000155564 7001_ $$00000-0002-4700-272X$$aSonner, Jana K.$$b13
000155564 7001_ $$avon Landenberg, Anna$$b14
000155564 7001_ $$aCichon, Frederik$$b15
000155564 7001_ $$aAslan, Katrin$$b16
000155564 7001_ $$aTrobisch, Tim$$b17
000155564 7001_ $$00000-0001-7142-4116$$aSchirmer, Lucas$$b18
000155564 7001_ $$aAbu-Sammour, Denis$$b19
000155564 7001_ $$aKessler, Tobias$$b20
000155564 7001_ $$aRatliff, Miriam$$b21
000155564 7001_ $$aSchrimpf, Daniel$$b22
000155564 7001_ $$00000-0001-5441-1962$$aSahm, Felix$$b23
000155564 7001_ $$00000-0003-0802-6451$$aHopf, Carsten$$b24
000155564 7001_ $$00000-0002-9258-3033$$aHeiland, Dieter H.$$b25
000155564 7001_ $$aSchnell, Oliver$$b26
000155564 7001_ $$aBeck, Jürgen$$b27
000155564 7001_ $$0P:(DE-2719)9000034$$aBöttcher, Chotima$$b28$$udzne
000155564 7001_ $$00000-0003-4795-6053$$aFernandez-Zapata, Camila$$b29
000155564 7001_ $$0P:(DE-2719)2811122$$aPriller, Josef$$b30$$udzne
000155564 7001_ $$aHeiland, Sabine$$b31
000155564 7001_ $$aGutcher, Ilona$$b32
000155564 7001_ $$aQuintana, Francisco J.$$b33
000155564 7001_ $$00000-0002-5863-540X$$avon Deimling, Andreas$$b34
000155564 7001_ $$00000-0002-6171-634X$$aWick, Wolfgang$$b35
000155564 7001_ $$00000-0002-0349-1955$$aPrinz, Marco$$b36
000155564 7001_ $$00000-0002-4746-887X$$aPlatten, Michael$$b37$$eCorresponding author
000155564 773__ $$0PERI:(DE-600)3005299-3$$a10.1038/s43018-021-00201-z$$gVol. 2, no. 7, p. 723 - 740$$n7$$p723 - 740$$tNature cancer$$v2$$x2662-1347$$y2021
000155564 8564_ $$uhttps://www.nature.com/articles/s43018-021-00201-z
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