Decreased Serum Tryptophan Concentration Predicts Poor Prognosis in Malignant Melanoma Patients

Abstract

Background: Indoleamine (2,3)-dioxygenase (IDO) catalyses the initial, rate-limiting step in the degradation of the essential amino acid tryptophan. Via tryptophan deprivation, IDO activity suppresses T cell proliferation and differentiation and is thought to be a fundamental immune escape mechanism for tumor cells. Objective and Methods: To investigate the potential role of tryptophan degradation as a prognostic marker, serum tryptophan and kynurenine concentrations and the kynurenine-to-tryptophan ratio (kyn/trp) in 87 patients with malignant melanoma were compared to the course of the disease and to concentrations of the immune activation marker neopterin. Results: Compared to 49 healthy volunteers, the melanoma patients presented with lower tryptophan levels due to accelerated degradation. This was especially true for the subgroups of patients with distant metastases (p = 0.01), though not in patients with lymph node metastases or in patients who had not yet progressed. There existed a positive correlation between kyn/trp and neopterin concentrations (r_s = 0.587, p <0.001). In patients who died due to dissemination of the tumor, median tryptophan concentrations were significantly decreased (p = 0.006) and kyn/trp (p = 0.03) and neopterin concentrations (p = 0.002) were higher compared to survivors. In addition, lower tryptophan concentrations as well as higher kyn/trp and neopterin concentrations predicted a shorter survival. Conclusion: Decreased serum tryptophan concentrations and elevated serum neopterin levels can be used as predictive markers for the future course in melanoma patients. Moreover, our data support previous speculations that a higher degree of IDO expression could play a crucial role for tumor progression.