Indoleamine 2,3-dioxygenase, Tregs and cancer

Curr Med Chem. 2011;18(15):2240-6. doi: 10.2174/092986711795656045.


The IDO pathway is implicated in a number of settings which lead to acquired peripheral tolerance. One such setting may be the functional tolerance displayed by tumor-bearing hosts toward tumor-associated antigens. Foxp3(+) Tregs are now recognized as a major contributor to tumor-induced immune suppression and functional tolerance. Emerging evidence links the IDO pathway with Treg biology at several points. The first is the ability of IDO-expressing DCs to drive the differentiation of naive CD4(+) T cells toward a Foxp3+ (inducible Treg) phenotype. The second link is the ability of IDO-expressing DCs to directly activate mature, pre-existing Tregs for markedly enhanced suppression of target cells. And the third link is the ability of IDO to prevent the inflammation-induced conversion ("reprogramming") of Tregs into pro-inflammatory T-helper-like cells in vivo. Taken together, these findings suggest that IDO may represent an important regulatory checkpoint influencing Treg activity: both by stabilizing and augmenting the suppressive phenotype, and by preventing Treg reprogramming into non-suppressive helper-like cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Enzyme Inhibitors / pharmacology
  • Forkhead Transcription Factors / immunology
  • Humans
  • Immune Tolerance
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / antagonists & inhibitors
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / immunology*
  • Interleukin-6 / immunology
  • Kynurenine / immunology
  • Neoplasms / enzymology*
  • Neoplasms / immunology*
  • Protein Serine-Threonine Kinases / immunology
  • T-Lymphocytes, Regulatory / enzymology
  • T-Lymphocytes, Regulatory / immunology*


  • Enzyme Inhibitors
  • Forkhead Transcription Factors
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Interleukin-6
  • Kynurenine
  • Protein Serine-Threonine Kinases