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Tryptophan metabolism drives dynamic immunosuppressive myeloid states in IDH-mutant gliomas

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Tryptophan metabolism drives dynamic immunosuppressive myeloid states in IDH-mutant gliomas. / Friedrich, Mirco; Sankowski, Roman; Bunse, Lukas; Kilian, Michael; Green, Edward; Ramallo Guevara, Carina; Pusch, Stefan; Poschet, Gernot; Sanghvi, Khwab; Hahn, Markus; Bunse, Theresa; Münch, Philipp; Gegner, Hagen; Sonner, Jana; von Landenberg, Anna; Cichon, Frederik; Aslan, Katrin; Trobisch, Tim; Schirmer, Lucas; Abu-Sammour, Denis; Kessler, Tobias; Ratliff, Miriam; Schrimpf, Daniel; Sahm, Felix; Hopf, Carsten; Heiland, Dieter; Schnell, Oliver; Beck, Jürgen; Böttcher, Chotima; Fernandez-Zapata, Camila; Priller, Josef; Heiland, Sabine; Gutcher, Ilona; Quintana, Francisco; von Deimling, Andreas; Wick, Wolfgang; Prinz, Marco; Platten, Michael.

In: NAT CANCER, Vol. 2, 24.05.2021, p. 723-740.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Friedrich, M, Sankowski, R, Bunse, L, Kilian, M, Green, E, Ramallo Guevara, C, Pusch, S, Poschet, G, Sanghvi, K, Hahn, M, Bunse, T, Münch, P, Gegner, H, Sonner, J, von Landenberg, A, Cichon, F, Aslan, K, Trobisch, T, Schirmer, L, Abu-Sammour, D, Kessler, T, Ratliff, M, Schrimpf, D, Sahm, F, Hopf, C, Heiland, D, Schnell, O, Beck, J, Böttcher, C, Fernandez-Zapata, C, Priller, J, Heiland, S, Gutcher, I, Quintana, F, von Deimling, A, Wick, W, Prinz, M & Platten, M 2021, 'Tryptophan metabolism drives dynamic immunosuppressive myeloid states in IDH-mutant gliomas', NAT CANCER, vol. 2, pp. 723-740. https://doi.org/10.1038/s43018-021-00201-z

APA

Friedrich, M., Sankowski, R., Bunse, L., Kilian, M., Green, E., Ramallo Guevara, C., Pusch, S., Poschet, G., Sanghvi, K., Hahn, M., Bunse, T., Münch, P., Gegner, H., Sonner, J., von Landenberg, A., Cichon, F., Aslan, K., Trobisch, T., Schirmer, L., ... Platten, M. (2021). Tryptophan metabolism drives dynamic immunosuppressive myeloid states in IDH-mutant gliomas. NAT CANCER, 2, 723-740. https://doi.org/10.1038/s43018-021-00201-z

Vancouver

Friedrich M, Sankowski R, Bunse L, Kilian M, Green E, Ramallo Guevara C et al. Tryptophan metabolism drives dynamic immunosuppressive myeloid states in IDH-mutant gliomas. NAT CANCER. 2021 May 24;2:723-740. https://doi.org/10.1038/s43018-021-00201-z

Bibtex

@article{33a2b62b45114ceb91aeaea1b784e896,
title = "Tryptophan metabolism drives dynamic immunosuppressive myeloid states in IDH-mutant gliomas",
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.",
author = "Mirco Friedrich and Roman Sankowski and Lukas Bunse and Michael Kilian and Edward Green and {Ramallo Guevara}, Carina and Stefan Pusch and Gernot Poschet and Khwab Sanghvi and Markus Hahn and Theresa Bunse and Philipp M{\"u}nch and Hagen Gegner and Jana Sonner and {von Landenberg}, Anna and Frederik Cichon and Katrin Aslan and Tim Trobisch and Lucas Schirmer and Denis Abu-Sammour and Tobias Kessler and Miriam Ratliff and Daniel Schrimpf and Felix Sahm and Carsten Hopf and Dieter Heiland and Oliver Schnell and J{\"u}rgen Beck and Chotima B{\"o}ttcher and Camila Fernandez-Zapata and Josef Priller and Sabine Heiland and Ilona Gutcher and Francisco Quintana and {von Deimling}, Andreas and Wolfgang Wick and Marco Prinz and Michael Platten",
year = "2021",
month = may,
day = "24",
doi = "https://doi.org/10.1038/s43018-021-00201-z",
language = "English",
volume = "2",
pages = "723--740",
journal = "NAT CANCER",
issn = "2662-1347",
publisher = "NATURE PUBLISHING GROUP",

}

RIS

TY - JOUR

T1 - Tryptophan metabolism drives dynamic immunosuppressive myeloid states in IDH-mutant gliomas

AU - Friedrich, Mirco

AU - Sankowski, Roman

AU - Bunse, Lukas

AU - Kilian, Michael

AU - Green, Edward

AU - Ramallo Guevara, Carina

AU - Pusch, Stefan

AU - Poschet, Gernot

AU - Sanghvi, Khwab

AU - Hahn, Markus

AU - Bunse, Theresa

AU - Münch, Philipp

AU - Gegner, Hagen

AU - Sonner, Jana

AU - von Landenberg, Anna

AU - Cichon, Frederik

AU - Aslan, Katrin

AU - Trobisch, Tim

AU - Schirmer, Lucas

AU - Abu-Sammour, Denis

AU - Kessler, Tobias

AU - Ratliff, Miriam

AU - Schrimpf, Daniel

AU - Sahm, Felix

AU - Hopf, Carsten

AU - Heiland, Dieter

AU - Schnell, Oliver

AU - Beck, Jürgen

AU - Böttcher, Chotima

AU - Fernandez-Zapata, Camila

AU - Priller, Josef

AU - Heiland, Sabine

AU - Gutcher, Ilona

AU - Quintana, Francisco

AU - von Deimling, Andreas

AU - Wick, Wolfgang

AU - Prinz, Marco

AU - Platten, Michael

PY - 2021/5/24

Y1 - 2021/5/24

N2 - 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.

AB - 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.

U2 - https://doi.org/10.1038/s43018-021-00201-z

DO - https://doi.org/10.1038/s43018-021-00201-z

M3 - SCORING: Journal article

VL - 2

SP - 723

EP - 740

JO - NAT CANCER

JF - NAT CANCER

SN - 2662-1347

ER -