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Serum Tryptophan and Kynurenine Concentrations as Parameters for Indoleamine 2,3-Dioxygenase Activity in Patients With Endometrial, Ovarian, and Vulvar Cancer
  1. Renske A. de Jong, MD*,
  2. Hans W. Nijman, MD, PhD*,
  3. H. Marike Boezen, PhD,
  4. Marcel Volmer, PhD,
  5. Klaske A. ten Hoor*,
  6. Jasper Krijnen,
  7. Ate G.J. van der Zee, MD, PhD*,
  8. Harry Hollema, MD, PhD§ and
  9. Ido P. Kema, PhD
  1. *Departments of Gynecologic Oncology,
  2. Departments of Epidemiology,
  3. Departments of Laboratory Medicine, and
  4. §Departments of Pathology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
  1. Address correspondence and reprint requests to Hans W. Nijman, MD, PhD, Department of Gynecologic Oncology, University Medical Center Groningen, PO 30.001, 9700 RB Groningen, The Netherlands. E-mail: h.w.nijman{at}


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.

  • Indoleamine 2,3-dioxygenase
  • Tryptophan
  • Endometrial cancer
  • Ovarian cancer
  • Vulvar cancer

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  • The authors did not receive funding for this study.

  • The authors declare that there are no conflicts of interest.