Serum Tryptophan and Kynurenine Concentrations as Parameters for Indoleamine 2,3-Dioxygenase Activity in Patients With Endometrial, Ovarian, and Vulvar Cancer

Objective: Indoleamine 2,3-dioxygenase (IDO) suppresses the function of T-lymphocytes and is involved in immune escape of cancers. Indoleamine 2,3-dioxygenase catalyzes the initial rate-limiting step in the degradation of the essential amino acid tryptophan. In this study, we investigated cancer-induced IDO activity in sera of endometrial, ovarian, and vulvar cancer patients. Methods: Concentrations of tryptophan and kynurenine were determined in pretreatment serum samples of patients with endometrial (n = 41), ovarian (n = 28), and vulvar cancer (n = 40) and compared to 19 healthy female controls. In serum of a subgroup of endometrial (n = 22), ovarian (n = 21), and vulvar (n = 21) cancer patients, tryptophan, kynurenine, and the kynurenine-to-tryptophan ratio (kyn/trp) were determined at different time points: preoperative, at clinical remission, and at the time of diagnosis of recurrent disease. Analyses were performed by an automated online solid-phase extraction-liquid chromatographic-tandem mass spectrometric method. Indoleamine 2,3-dioxygenase activity was estimated by calculating the kyn/trp ratio. Results: Kynurenine concentrations and the kyn/trp ratio were higher in preoperative serum of endometrial, ovarian, and vulvar cancer patients compared to controls (all: P < 0.001). Preoperative serum of ovarian cancer patients contained higher kynurenine concentrations (median, 2.53 mu M; interquartile range [IQR], 1.72-4.29 mu M) and a higher kyn/trp ratio (median, 39.3 mu mol/mmol; IQR, 26.5-61.7 mu mol/mmol) compared to serum collected at clinical remission (median, 2.02 mu M; IQR, 1.68-2.72 mu M, P = 0.035; and median, 29.9 mu mol/mmol; IQR, 23.4-38.9 mu mol/mmol, P = 0.005, respectively). Conclusions: Patients with endometrial, ovarian, and vulvar cancer have increased tryptophan degradation compared to controls resulting in higher serum kynurenine concentrations and a higher kyn/trp ratio. Our results suggest that IDO-induced immune escape may play an important role in these gynecologic cancers.