%0 Journal Article
%A Friedrich, Mirco
%A Sankowski, Roman
%A Bunse, Lukas
%A Kilian, Michael
%A Green, Edward
%A Ramallo Guevara, Carina
%A Pusch, Stefan
%A Poschet, Gernot
%A Sanghvi, Khwab
%A Hahn, Markus
%A Bunse, Theresa
%A Münch, Philipp
%A Gegner, Hagen M.
%A Sonner, Jana K.
%A von Landenberg, Anna
%A Cichon, Frederik
%A Aslan, Katrin
%A Trobisch, Tim
%A Schirmer, Lucas
%A Abu-Sammour, Denis
%A Kessler, Tobias
%A Ratliff, Miriam
%A Schrimpf, Daniel
%A Sahm, Felix
%A Hopf, Carsten
%A Heiland, Dieter H.
%A Schnell, Oliver
%A Beck, Jürgen
%A Böttcher, Chotima
%A Fernandez-Zapata, Camila
%A Priller, Josef
%A Heiland, Sabine
%A Gutcher, Ilona
%A Quintana, Francisco J.
%A von Deimling, Andreas
%A Wick, Wolfgang
%A Prinz, Marco
%A Platten, Michael
%T Tryptophan metabolism drives dynamic immunosuppressive myeloid states in IDH-mutant gliomas
%J Nature cancer
%V 2
%N 7
%@ 2662-1347
%C London
%I Nature Research
%M DZNE-2021-00742
%P 723 - 740
%D 2021
%X 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.
%K Brain Neoplasms: genetics
%K Glioma: genetics
%K Humans
%K Immunotherapy
%K Isocitrate Dehydrogenase: genetics
%K Tryptophan: therapeutic use
%K Tumor Microenvironment: genetics
%K Tryptophan (NLM Chemicals)
%K Isocitrate Dehydrogenase (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:35121943
%R 10.1038/s43018-021-00201-z
%U https://pub.dzne.de/record/155564