Tryptophan Metabolites as a Potential Tumor Marker

The kynurenine pathway of tryptophan metabolism converts the essential amino acid L-tryptophan into a number of biologically active metabolites such as kynurenine (Kyn), kynurenic acid, (hydroxykynurenine, and quinolinic acid. Indoleamine 2,3-dioxygenases (IDO1 and IDO2) and tryptophan 2,3-dioxygease (TDO) mediate the central route of tryptophan metabolism, which is related to the degradation of tryptophan and the accumulation of kynurenine pathway metabolites in the microenvironment. IDO1 is overexpressed in many cancers. IDO1 is thought to represent a major mechanism of the escape of tumor from the host immune system. Several strategies for targeting IDO1 is currently being assessed in multiple clinical trials. In addition to IDO1, we demonstrated that IDO2 is also an important immune regulator in the tumor microenvironment. In this presentation, we will address the important role of tryptophan-metabolizing enzymes in tumor microenvironment, and serum Kyn can be used as a biomarker for the prognosis and the rate of progression of several cancers. We demonstrated that serum Kyn is correlated with poor prognosis of several cancers such as leukemia/lymphoma. We will also address that quantification of tryptophan metabolites by our recently developed liquid chromatography-mass spectrometry (LC-MS) method can be applied to analyze changes in tryptophan metabolism in serum. Imbalances in tryptophan metabolism is implicated in diseases ranging from cancer to neuropsychiatric diseases. We believe that this method could offers a novel approach to develop potential biomarkers for diagnosis, assessment and prognosis of the diseases.