Publication Date:
2018-11-29
Description:
Background: Indoleamine 2,3-dioxygenase (IDO) is an intracellular enzyme that catalyzes the initial rate-limiting step in Tryptophan (Trp) degradation along the Kynurenine pathway. Trp can be catabolized by tryptophan hydroxylase into serotonin (Ser) or alternatively, by IDO and tryptophan-2,3-dioxygenase (TDO) into Kynurenine (Kyn). A variety of human tumors have been shown to express an active IDO which leads to the induction of immune tolerance and malignant cell survival (Mellor et al, 1999). Elevated IDO activity within tumor microenvironment impairs the function of antigen specific T cells and suppresses the anti-tumor immune response, while in tumor-draining lymph nodes an active IDO inhibits the antigen presentation reducing the population of antigen-specific T cells and stimulates regulatory T cells (Treg) activation (Curti et al. 2009). IDO overexpression has been correlated with poor prognosis in a number of human solid tumors including ovarian, endometrial and colon carcinoma (Okamoto et al. 2005, Ino et al. 2006, Brandacher et al. 2006). In hematological malignancies, such as AML and DLBCL, IDO expression has also shown significant prognostic value (Folgiero et al. 2014, Ninomiya et al. 2011). Currently, our understanding of the role of IDO in multiple myeloma (MM) is limited to a few existing studies correlating the abundance of selected IDO pathway metabolites with the disease (Bonanno et al. 2012, Zdzisinska et al. 2010). We hypothesize that IDO activity correlates with the disease onset and progression in MM patients. Methods: We quantified the levels of Trp, Kyn, and Ser in human serum by mass spectrometry using the Biocrates AbsoluteIDQ p180 kit. Analysis was performed using MetaboAnalyst 3.0 and Graphpad prism software. The serum samples derived from healthy donors and MM patients were obtained commercially. Results: We found significantly reduced levels of Trp (n=13, p
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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