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Expert Opin Ther Targets. 2005 Aug;9(4):831-49.

Indoleamine 2,3-dioxygenase in cancer: targeting pathological immune tolerance with small-molecule inhibitors.

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1
Lankenau Institute for Medical Research, Wynnewood, PA 19096, USA. mullera@mlhs.org

Abstract

Indoleamine 2,3-dioxygenase (IDO) is an interferon (IFN)-gamma-inducible, extrahepatic enzyme that catalyses the initial and rate-limiting step in the degradation of the essential amino acid tryptophan. Elevated tryptophan catabolism mediated by IDO is associated with a wide variety of human cancers and has historically been thought to be a tumoricidal consequence of IFN-gamma exposure. Evidence of a physiological requirement for IDO activity in protecting the allogeneic fetus from rejection by the maternal immune system has stimulated a radical shift in thinking about the role of IDO in cancer. Evidence now suggests that tumours can exploit IDO-mediated peripheral tolerance to promote immune escape. This review summarises key studies that implicate IDO as an important mediator of peripheral immune tolerance as well as the development of a promising new anticancer modality that incorporates the use of IDO inhibitors. The second part focuses on the current state of development of IDO inhibitory compounds as potential pharmaceutical agents.

PMID:
16083346
DOI:
10.1517/14728222.9.4.831
[Indexed for MEDLINE]
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