Tryptamine and dimethyltryptamine inhibit indoleamine 2, 3 dioxygenase and increase the tumor-reactive effect of peripheral blood mononuclear cells

Department of Clinical Chemistry and Toxicology, Faculty of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, BrazilIndoleamine2,3-dioxygenase(IDO)isaninterferon-g(IFN-g)–inducedtryptophan-degradingenzyme,producingkynurenine(KYN)thatpartic-ipates in the mechanism oftumorimmune tolerance. Thus, IDO inhibition hasbeen considereda strategyfor anticancer therapy. The aim of thisstudywas to identify whether the metabolites originated from the competitive routes oftryptophan metabolism, such as the serotonergic or N,N-dimethyltryptamine(DMT)pathways,haveinhibitoryeffectsonrecombinanthumanIDO(rhIDO)activity.Serotoninandmelatoninhadnoeffect; onthe other hand, tryptamine(TRY) andDMTmodulatedthe activity ofrhIDOas classical non-competitiveinhibitors, with Ki valuesof 156 and 506 mM, respectively. This inhibitory effect was also observed on constitutively expressed or IFN-g–induced IDO in the A172human glioma cell line. TRY and DMT increased the cytotoxic activity of peripheral blood mononuclear cells (PBMCs) in co-culture assays.We conclude that the IDO inhibition by TRY and DMT contributed to a more effective tumor-reactive response by the PBMCs. Copyright ©2013 John Wiley & Sons, Ltd.key words—immune escape; kynurenine pathway; tolerance; tryptophan metabolism; tumor growth