Cancer Immunotherapy by Targeting IDO1/TDO and Their Downstream Effectors

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2015 Jan 29

PMID 25628622

Citations 202

Authors

Michael Platten

Nikolaus von Knebel Doeberitz

Iris Oezen

Wolfgang Wick

Katharina Ochs

Affiliations

Soon will be listed here.

Abstract

The tryptophan (TRP) to kynurenine (KYN) metabolic pathway is now firmly established as a key regulator of innate and adaptive immunity. A plethora of preclinical models suggests that this immune tolerance pathway - driven by the key and rate-limiting enzymes indoleamine-2,3-dioxygenase and TRP-2,3-dioxygenase - is active in cancer immunity, autoimmunity, infection, transplant rejection, and allergy. Drugs targeting this pathway, specifically indoleamine-2,3-dioxygenase, are already in clinical trials with the aim at reverting cancer-induced immunosuppression. In the past years, there has been an increase in our understanding of the regulation and downstream mediators of TRP metabolism, such as the aryl hydrocarbon receptor as a receptor for KYN and kynurenic acid. This more detailed understanding will expand our opportunities to interfere with the pathway therapeutically on multiple levels. Here, we discuss the perspective of targeting TRP metabolism at these different levels based on reviewing recent insight into the regulation of TRP metabolism and its downstream effectors.

Citing Articles

Targeting Metabolic Vulnerabilities to Combat Drug Resistance in Cancer Therapy.

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Targeting the kynurenine pathway: another therapeutic opportunity in the metabolic crosstalk between cancer and immune cells.

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Kynurenines as a Novel Target for the Treatment of Inflammatory Disorders.

Mor A, Tankiewicz-Kwedlo A, Ciwun M, Lewkowicz J, Pawlak D Cells. 2024; 13(15.

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