Indoleamine-2,3-dioxygenase (IDO) metabolic activity is detrimental for cervical cancer patient survival

Debbie M. Ferns, Ido P. Kema, Marrije R. Buist, Hans W. Nijman, Gemma G. Kenter, Ekaterina S. Jordanova*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

48 Citations (Scopus)

Abstract

The expression of the immunomodulating enzyme indoleamine-2,3-dioxygenase (IDO) suppresses T-lymphocyte function, thus correlating with poor survival in a variety of cancer patients. IDO degrades the essential amino acid tryptophan leading to immunosuppressive kynurenines production. In the present study, concentrations of tryptophan, 3-hydroxykynurenine, and kynurenine were measured in pre-treatment serum samples of 251 cervical cancer patients by a mass-spectrometric method (XLC-MS/MS) and IDO activity determined by the kynurenine/tryptophan (Kyn/Trp) ratio. A low concentration of tryptophan was found to be significantly associated with tumors greater than 4 cm and lymph node metastatic spread. Furthermore, significant positive correlations were found between high concentrations of the tryptophan metabolites kynurenine and 3-hydroxykynurenine and advanced disease stage (FIGO > IIA) and lymph node metastases. High levels of kynurenine were further associated with parametrial invasion and tumor size. A high Kyn/Trp ratio was related to lymph node metastasis, FIGO stage, tumor size, parametrial invasion and poor disease-specific survival. These results suggest that IDO activation is linked to poor clinicopathological parameters and worse survival in cervical cancer, warranting the use of IDO inhibitors in future clinical trials.

Original languageEnglish
Article number981457
Number of pages7
JournalOncoImmunology
Volume4
Issue number2
DOIs
Publication statusPublished - Feb-2015

Keywords

  • cervical cancer
  • IDO
  • kynurenine
  • Kyn/Trp ratio
  • tryptophan
  • INDOLEAMINE 2,3-DIOXYGENASE EXPRESSION
  • REGULATORY T-CELLS
  • LUNG-CANCER
  • TRYPTOPHAN CATABOLITES
  • DISEASE PROGRESSION
  • KYNURENINE PATHWAY
  • SUPPRESSOR-CELLS
  • PROGNOSTIC VALUE
  • IMMUNE ESCAPE
  • INFLAMMATION

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