Tryptophan metabolism in brain tumors — IDO and beyond

Michael Platten; Mirco Friedrich; Derek A. Wainwright; Verena Panitz; Christiane A. Opitz

doi:10.1016/j.coi.2021.03.005

Tryptophan metabolism in brain tumors — IDO and beyond

Michael Platten, Mirco Friedrich, Derek A. Wainwright, Verena Panitz, Christiane A. Opitz

Neurological Surgery

Research output: Contribution to journal › Review article › peer-review

28 Scopus citations

Abstract

Metabolism of the essential amino acid tryptophan is a key metabolic pathway that restricts antitumor immunity and is a drug development target for cancer immunotherapy. Tryptophan metabolism is active in brain tumors including gliomas and promotes a malignant phenotype and contributes to the immunosuppressive tumor microenvironment. In recent years, improved understanding of the regulation and downstream function of tryptophan metabolism has been significantly expanded beyond the initial in vitro observation that the enzyme indoleamine-2,3-dioxygenase 1 (IDO1) promotes the depletion of intracellular tryptophan. Here, we revisit the specific roles of tryptophan metabolites in regulating brain functioning and neuronal integrity as well as in the context of brain tumors.

Original language	English (US)
Pages (from-to)	57-66
Number of pages	10
Journal	Current Opinion in Immunology
Volume	70
DOIs	https://doi.org/10.1016/j.coi.2021.03.005
State	Published - Jun 2021

Funding

This work was supported by grants from the German Cancer Aid ( 70113515 ) and the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) ( 406052676 ; PL-315/5-1) to M.P. This work was supported in part by National Institutes of Health (NIH) P50 CA221747 (D.A.W.), NIH R01 NS097851 (D.A.W.), NIH K02 AG068617 (D.A.W.), BrainUp grant 2136 (D.A.W.), the Gail Boyter Magness (GBM) Foundation (D.A.W.), the Grace Giving Foundation (D.A.W.), the Stephen Coffman Charitable Trust (D.A.W.), and the 5 for the Fight organization (D.A.W.). V.P. was supported by the DKFZ Clinician Scientist Program and the Dieter Morszeck Foundation . M.F. is member of the MD/PhD program at Heidelberg University. M.F. received fellowships by the Heidelberg Biosciences International Graduate School (HBIGS), the German Academic Exchange Service (DAAD) and the Excellence Initiative of the German Council of Science and Humanities and the German Research Foundation (DFG). M.P. and C.A.O. were supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)–Project-ID 404521405, SFB 1389–UNITE Glioblastoma.

ASJC Scopus subject areas

Immunology and Allergy
Immunology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.coi.2021.03.005

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title = "Tryptophan metabolism in brain tumors — IDO and beyond",

abstract = "Metabolism of the essential amino acid tryptophan is a key metabolic pathway that restricts antitumor immunity and is a drug development target for cancer immunotherapy. Tryptophan metabolism is active in brain tumors including gliomas and promotes a malignant phenotype and contributes to the immunosuppressive tumor microenvironment. In recent years, improved understanding of the regulation and downstream function of tryptophan metabolism has been significantly expanded beyond the initial in vitro observation that the enzyme indoleamine-2,3-dioxygenase 1 (IDO1) promotes the depletion of intracellular tryptophan. Here, we revisit the specific roles of tryptophan metabolites in regulating brain functioning and neuronal integrity as well as in the context of brain tumors.",

author = "Michael Platten and Mirco Friedrich and Wainwright, {Derek A.} and Verena Panitz and Opitz, {Christiane A.}",

note = "Funding Information: This work was supported by grants from the German Cancer Aid ( 70113515 ) and the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) ( 406052676 ; PL-315/5-1) to M.P. This work was supported in part by National Institutes of Health (NIH) P50 CA221747 (D.A.W.), NIH R01 NS097851 (D.A.W.), NIH K02 AG068617 (D.A.W.), BrainUp grant 2136 (D.A.W.), the Gail Boyter Magness (GBM) Foundation (D.A.W.), the Grace Giving Foundation (D.A.W.), the Stephen Coffman Charitable Trust (D.A.W.), and the 5 for the Fight organization (D.A.W.). V.P. was supported by the DKFZ Clinician Scientist Program and the Dieter Morszeck Foundation . M.F. is member of the MD/PhD program at Heidelberg University. M.F. received fellowships by the Heidelberg Biosciences International Graduate School (HBIGS), the German Academic Exchange Service (DAAD) and the Excellence Initiative of the German Council of Science and Humanities and the German Research Foundation (DFG). M.P. and C.A.O. were supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)–Project-ID 404521405, SFB 1389–UNITE Glioblastoma. Publisher Copyright: {\textcopyright} 2021 Elsevier Ltd",

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N2 - Metabolism of the essential amino acid tryptophan is a key metabolic pathway that restricts antitumor immunity and is a drug development target for cancer immunotherapy. Tryptophan metabolism is active in brain tumors including gliomas and promotes a malignant phenotype and contributes to the immunosuppressive tumor microenvironment. In recent years, improved understanding of the regulation and downstream function of tryptophan metabolism has been significantly expanded beyond the initial in vitro observation that the enzyme indoleamine-2,3-dioxygenase 1 (IDO1) promotes the depletion of intracellular tryptophan. Here, we revisit the specific roles of tryptophan metabolites in regulating brain functioning and neuronal integrity as well as in the context of brain tumors.

AB - Metabolism of the essential amino acid tryptophan is a key metabolic pathway that restricts antitumor immunity and is a drug development target for cancer immunotherapy. Tryptophan metabolism is active in brain tumors including gliomas and promotes a malignant phenotype and contributes to the immunosuppressive tumor microenvironment. In recent years, improved understanding of the regulation and downstream function of tryptophan metabolism has been significantly expanded beyond the initial in vitro observation that the enzyme indoleamine-2,3-dioxygenase 1 (IDO1) promotes the depletion of intracellular tryptophan. Here, we revisit the specific roles of tryptophan metabolites in regulating brain functioning and neuronal integrity as well as in the context of brain tumors.

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Tryptophan metabolism in brain tumors — IDO and beyond

Abstract

Funding

ASJC Scopus subject areas

UN SDGs

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