| Literature DB >> 22308364 |
Luc Pilotte1, Pierre Larrieu, Vincent Stroobant, Didier Colau, Eduard Dolusic, Raphaël Frédérick, Etienne De Plaen, Catherine Uyttenhove, Johan Wouters, Bernard Masereel, Benoît J Van den Eynde.
Abstract
Tryptophan catabolism mediated by indoleamine 2,3-dioxygenase (IDO1) is an important mechanism of peripheral immune tolerance contributing to tumoral immune resistance, and IDO1 inhibition is an active area of drug development. Tryptophan 2,3-dioxygenase (TDO) is an unrelated hepatic enzyme that also degrades tryptophan along the kynurenine pathway. Here, we show that enzymatically active TDO is expressed in a significant proportion of human tumors. In a preclinical model, TDO expression by tumors prevented their rejection by immunized mice. We developed a TDO inhibitor, which, upon systemic treatment, restored the ability of mice to reject TDO-expressing tumors. Our results describe a mechanism of tumoral immune resistance based on TDO expression and establish proof-of-concept for the use of TDO inhibitors in cancer therapy.Entities:
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Year: 2012 PMID： 22308364 PMCID： PMC3289319 DOI： 10.1073/pnas.1113873109
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205