title: Indoleamine 2,3-dioxygenase in cancer: targeting pathological immune tolerance with small-molecule inhibitors.
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.
authors.affiliation: Lankenau Institute for Medical Research, Wynnewood, PA 19096, USA. mullera@mlhs.org
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Muller
authors.forename: William P
authors.initials: WP
authors.lastname: Malachowski
authors.forename: George C
authors.initials: GC
authors.lastname: Prendergast
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects* / Q000276:immunology; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors* / Q000276:immunology; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014364:Tryptophan / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D014364:Tryptophan