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

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.

journal_name

Target Oncol

journal_title

Targeted oncology

authors

Davar D,Bahary N

doi

10.1007/s11523-017-0547-9

subject

Has Abstract

pub_date

2018-04-01 00:00:00

pages

125-140

issue

2

eissn

1776-2596

issn

1776-260X

pii

10.1007/s11523-017-0547-9

journal_volume

13

pub_type

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