Cancer Immunotherapy: Chapter 33. IDO Pathway: Effect on Foxp3+ Tregs and Cancer

Cancer Immunotherapy: Chapter 33. IDO Pathway: Effect on Foxp3+ Tregs and Cancer
ISBN-10
012805929X
ISBN-13
9780128059296
Series
Cancer Immunotherapy
Category
Medical
Pages
684
Language
English
Published
2013-06-04
Publisher
Elsevier Inc. Chapters
Authors
David H. Munn, Andrew L. Mellor

Description

Indoleamine 2,3-dioxygenase (IDO) is a metabolic pathway implicated in a number of settings that lead to acquired peripheral tolerance. IDO may also participate in the functional tolerance of the immune system towards tumors. Foxp3+ Tregs are major contributors to tumor-induced immune suppression, and emerging evidence links the IDO pathway with Treg activation. IDO-expressing dendritic cells (DCs) can drive the differentiation of naive CD4+ T cells into Foxp3+ Tregs. IDO+ DCs can also directly activate mature, preformed Tregs to mediate enhanced suppression. In experimental models, IDO also stabilizes the suppressive Treg phenotype and prevents inflammation-induced reprogramming of Tregs into pro-inflammatory (T-helper-like) cells. IDO may thus represent an important regulatory checkpoint that enhances Treg activity in tumor-bearing hosts. Drugs that target the IDO pathway may assist in reducing Treg-mediated suppression during antitumor immunotherapy.

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