title: Indoleamine 2,3-dioxygenase, Tregs and cancer.
abstract: 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.
authors.affiliation: Immunotherapy Program, Medical College of Georgia, Augusta, GA 30912, USA. dmunn@georgiahealth.edu
authors.forename: D H
authors.initials: DH
authors.lastname: Munn
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051858:Forkhead Transcription Factors / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology; D007737:Kynurenine / Q000276:immunology; D009369:Neoplasms / Q000201:enzymology* / Q000276:immunology*; D017346:Protein Serine-Threonine Kinases / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000201:enzymology / Q000276:immunology*
chemical_list: D004791:Enzyme Inhibitors; D051858:Forkhead Transcription Factors; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D015850:Interleukin-6; D007737:Kynurenine; D017346:Protein Serine-Threonine Kinases