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@ARTICLE{Friedrich:155564,
author = {Friedrich, Mirco and Sankowski, Roman and Bunse, Lukas and
Kilian, Michael and Green, Edward and Ramallo Guevara,
Carina and Pusch, Stefan and Poschet, Gernot and Sanghvi,
Khwab and Hahn, Markus and Bunse, Theresa and Münch,
Philipp and Gegner, Hagen M. and Sonner, Jana K. and von
Landenberg, Anna and Cichon, Frederik and Aslan, Katrin and
Trobisch, Tim and Schirmer, Lucas and Abu-Sammour, Denis and
Kessler, Tobias and Ratliff, Miriam and Schrimpf, Daniel and
Sahm, Felix and Hopf, Carsten and Heiland, Dieter H. and
Schnell, Oliver and Beck, Jürgen and Böttcher, Chotima and
Fernandez-Zapata, Camila and Priller, Josef and Heiland,
Sabine and Gutcher, Ilona and Quintana, Francisco J. and von
Deimling, Andreas and Wick, Wolfgang and Prinz, Marco and
Platten, Michael},
title = {{T}ryptophan metabolism drives dynamic immunosuppressive
myeloid states in {IDH}-mutant gliomas},
journal = {Nature cancer},
volume = {2},
number = {7},
issn = {2662-1347},
address = {London},
publisher = {Nature Research},
reportid = {DZNE-2021-00742},
pages = {723 - 740},
year = {2021},
abstract = {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.},
keywords = {Brain Neoplasms: genetics / Glioma: genetics / Humans /
Immunotherapy / Isocitrate Dehydrogenase: genetics /
Tryptophan: therapeutic use / Tumor Microenvironment:
genetics / Tryptophan (NLM Chemicals) / Isocitrate
Dehydrogenase (NLM Chemicals)},
cin = {Clinical Study Team Berlin 1 ; AG Priller},
ddc = {610},
cid = {I:(DE-2719)5000007},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:35121943},
doi = {10.1038/s43018-021-00201-z},
url = {https://pub.dzne.de/record/155564},
}