title: Serum tryptophan and kynurenine concentrations as parameters for indoleamine 2,3-dioxygenase activity in patients with endometrial, ovarian, and vulvar cancer.
abstract: 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 μM; interquartile range [IQR], 1.72-4.29 μM) and a higher kyn/trp ratio (median, 39.3 μmol/mmol; IQR, 26.5-61.7 μmol/mmol) compared to serum collected at clinical remission (median, 2.02 μM; IQR, 1.68-2.72 μM, P = 0.035; and median, 29.9 μmol/mmol; IQR, 23.4-38.9 μmol/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.
authors: Department of Gynecologic Oncology, University of Groningen, Groningen, The Netherlands.
authors: Renske A
authors: RA
authors: de Jong
authors: Hans W
authors: HW
authors: Nijman
authors: H Marike
authors: HM
authors: Boezen
authors: Marcel
authors: M
authors: Volmer
authors: Klaske A
authors: KA
authors: Ten Hoor
authors: Jasper
authors: J
authors: Krijnen
authors: Ate G J
authors: AG
authors: van der Zee
authors: Harry
authors: H
authors: Hollema
authors: Ido P
authors: IP
authors: Kema
mesh_terms: D000328:Adult; D000368:Aged; D000418:Albumins / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005833:Genital Neoplasms, Female / Q000097:blood / Q000201:enzymology*; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism*; D007737:Kynurenine / Q000097:blood*; D008875:Middle Aged; D014364:Tryptophan / Q000097:blood*
chemical_list: D000418:Albumins; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007737:Kynurenine; D014364:Tryptophan