Enhanced tryptophan degradation in patients with ovarian carcinoma correlates with several serum soluble immune activation markers.
Tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) represents an antimicrobial and antitumoral immune effector mechanism, but IDO also suppresses T-cell responses and thus can cause immune system failure. Therefore, IDO was proposed as an immunoescape mechanism of tumor cells. Compared to healthy controls, accelerated tryptophan degradation was observed in the blood of 20 patients with ovarian carcinoma as is reflected by an increased kynurenine to tryptophan ratio (kyn/trp) which allows an estimate of IDO activity. Higher FIGO stage but not tumor grading was associated with a higher rate of tryptophan degradation. Kyn/trp correlated strongly with concentrations of cytokine IL-6, of soluble interleukin-2 receptor-α and 75 kDa TNF-α receptor and of the macrophage marker neopterin (all p<0.001 or p<0.01) but not with TNF-α. Findings further supports the concept that increased IDO activity in ovarian cancer patients relates to immune activation pathways. Accordingly, accelerated tryptophan degradation appears to represent an immune escape mechanism. However IDO activity is not necessarily a spontaneous activity of ovarian cancer cells rather it is elicited by the activated immune system although an additional spontaneous activity of tumor cells cannot be ruled out.
Sperner-Unterweger
Barbara
B
Department of Psychiatry, Innsbruck Medical University, 6020 Innsbruck, Austria.
Neurauter
Gabriele
G
Klieber
Martin
M
Kurz
Katharina
K
Meraner
Verena
V
Zeimet
Alain
A
Fuchs
Dietmar
D
D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism*; D053645:Interleukin-2 Receptor alpha Subunit / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007737:Kynurenine / Q000097:blood*; D008875:Middle Aged; D019798:Neopterin / Q000097:blood; D010051:Ovarian Neoplasms / Q000097:blood / Q000276:immunology* / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D014364:Tryptophan / Q000097:blood / Q000378:metabolism*
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D053645:Interleukin-2 Receptor alpha Subunit; D015850:Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; D007737:Kynurenine; D019798:Neopterin; D014364:Tryptophan