IDO Pathway: Effect on Foxp3+ Tregs and Cancer

David H. Munn, Andrew L. Mellor

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Scopus citations

Abstract

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.

Original languageEnglish (US)
Title of host publicationCancer Immunotherapy
Subtitle of host publicationImmune Suppression and Tumor Growth: Second Edition
PublisherElsevier Inc.
Pages583-596
Number of pages14
ISBN (Print)9780123942968
DOIs
StatePublished - Jan 1 2013

Keywords

  • Dendritic cells
  • Foxp3
  • IDO
  • Regulatory T cells
  • Tumor immunology

ASJC Scopus subject areas

  • Dentistry(all)
  • Medicine(all)

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    Munn, D. H., & Mellor, A. L. (2013). IDO Pathway: Effect on Foxp3+ Tregs and Cancer. In Cancer Immunotherapy: Immune Suppression and Tumor Growth: Second Edition (pp. 583-596). Elsevier Inc.. https://doi.org/10.1016/B978-0-12-394296-8.00033-6