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

Authors: Muller, Alexander J; Malachowski, William P; Prendergast, George C

Source: Expert Opinion on Therapeutic Targets, Volume 9, Number 4, 1 August 2005 , pp. 831-849(19)

Publisher: Informa Healthcare

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Abstract:

Indoleamine 2,3-dioxygenase (IDO) is an interferon (IFN)--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- 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 phar-maceutical agents.
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