The main objective of the present investigation was to study the urinary
neopterin excretion in the context of the activation of the adaptive cellular immune system at the
tumor site. For this purpose, we compared pre-treatment urinary
neopterin levels measured in 92
ovarian cancer patients, with intratumoral levels of
mRNA transcripts from factors either involved in the adaptive antitumor immune defense (CD3, IFN-γ, IRF-1, IRF-2, SOCS1 and iNOS) or immune tolerance (FoxP3). This study did not reveal an association between urinary
neopterin and one of these investigated "on
tumor site transcripts". From all the factors reflecting the magnitude of the local adaptive antitumor response, intratumoral IRF-1 expression above the edge of the 25th percentile was found to predict most reliably favorable progression-free (median 34 months vs. 10 months; p < 0.001) and overall (median 52 months vs. 16 months; p < 0.001) survival. In contrast, pre-treatment urinary
neopterin excretion above 275 μmol/mol
creatinine, which indicates an unspecific activation of the innate immune system, was associated with a very poor overall survival with a median of only 11 months when compared with a median overall survival of 40 months in patients with lower urinary
neopterin excretion (p = 0.021). Interestingly, the considerable survival benefit in patients with high IRF-1-expressing
cancers was completely abrogated as well for progression-free as for overall survival when urinary
neopterin concentrations were found to be concomitantly elevated. These findings demonstrate that in ovarian
carcinomas the unspecific "
cancer-related
inflammation" contributes to a significant subversion of the adaptive antitumor immune defense mounted at the
tumor site.