Tryptophan degradation in patients with gynecological cancer correlates with immune activation.
Cancer Lett. 2005 Jun 8;223(2):323-9. Epub 2004 Dec 8. PMID: 15896467
Institute of Medical Chemistry and Biochemistry, Innsbruck Medical University, Fritz Pregl Strasse 3, A-6020 Innsbruck, Austria.
Tryptophan degradation by the enzyme indoleamine-(2,3)-dioxy genase (IDO) and neopterin production are induced within cellular immune activation by stimulation of monocyte-derived macrophages and dendritic cells with cytokine interferon-gamma. Deprivation of tryptophan represents an important antimicrobial and antitumoral immune defence mechanism but it also suppresses T-cell proliferation. Recently tryptophan degradation by tumor cells was proposed as strategy to escape immune response. In this study the relationship between tryptophan degradation and immune activation was examined in 20 patients with gynecological cancer. Concentrations of tryptophan and kynurenine were measured by HPLC in sera of patients, and to estimate IDO activity, the kynurenine to tryptophan ratio was calculated. In parallel, neopterin concentrations were measured by ELISA. Tryptophan concentrations (median, interquartile range: 43.5, 31.2-56.3 microM) were lower in patients with gynecological cancer compared to healthy individuals of similar age (53.5, 47.0-64.2 microM; P<0.05). Kynurenine concentrations (median: 1.91 vs. 1.73 microM in controls) and kyn/trp (median: 41 vs. 35 micromol/mmol in controls) were slightly higher in patients, but not significantly different. Neopterin concentrations were significantly higher in patients (median: 10.8 vs. 7.0 nM in controls; P<0.05) and correlated with the kynurenine per tryptophan ratio (r(s)=0.555; P<0.02). In conclusion, tryptophan degradation is detectable in patients with gynecological cancer. The relationship between kyn/trp and neopterin concentrations indicates that cellular immune activation rather than tumor-mediated IDO-activity is responsible (228 words).