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Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Indoleamine 2,3-dioxygenase, Tregs and Cancer

Author(s): D. H. Munn

Volume 18, Issue 15, 2011

Page: [2240 - 2246] Pages: 7

DOI: 10.2174/092986711795656045

Price: $65


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.

Keywords: Regulatory T cells, Foxp3, IDO, dendritic cells, tumor immunology, peripheral tolerance, tumor-induced immune suppression, Treg biology, CD4+ T cells, inducible Treg

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