Modulating Tumor Immunology by Inhibiting Indoleamine 2,3-Dioxygenase (IDO): Recent Developments and First Clinical Experiences

Review Article

Abstract

Indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) catalyze the first rate-limiting step in the oxidative metabolism of compounds containing indole rings, including the transformation of the essential amino acid L-tryptophan to N-formyl-L-kynurenine. Through direct and indirect means, IDO exerts both tolerogenic and pro-inflammatory effects and has a profound immunoregulatory role in the tumor microenvironment. Although the role of IDO in mediating peripheral acquired immunologic tolerance has been known for some time, its role in tumorigenesis and the subversion of anti-tumor immunity have only recently been appreciated. Small-molecule inhibitors of IDO1 and TDO are being evaluated as single agents and in combination with immune checkpoint blockade in a host of advanced cancers. In this review, we delineate the tolerogenic and pro-inflammatory effects of IDO as it relates to immune escape and discuss current clinical progress in this area.

Notes

Compliance with Ethical Standards

Funding

D.D. is supported by the Conquer Cancer Foundation/Genentech BioOncology™ Young Investigator Award (YIA).

Conflict of Interest

Diwakar Davar has received grants or clinical trial support from Merck, Incyte, Checkmate Pharmaceuticals, and Bristol-Myers Squibb, and participated in advisory boards for Incyte. Nathan Bahary has grants pending from Pfizer, and participated in advisory boards for Celgene.

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Medicine, Division of Hematology-OncologyUniversity of Pittsburgh Medical CenterPittsburghUSA

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