Urinary neopterin does not reflect the local antitumor immune milieu in ovarian cancer.
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.
Zeimet
Alain G
AG
Department of Obstetrics and Gynecology, Innsbruck Medical University, Anichstrasse 35, 6020, Innsbruck, Austria. alain.zeimet@i-med.ac.at
Reimer
Daniel
D
Schwentner
Lukas
L
Fuchs
Dietmar
D
Wolf
Dominik
D
Fuith
Lothar C
LC
Fiegl
Heidi
H
Doppler
Wolfgang
W
Concin
Nicole
N
Daxenbichler
Günter
G
Marth
Christian
C
D056704:Adaptive Immunity; D000368:Aged; D005260:Female; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000235:genetics; D007371:Interferon-gamma / Q000502:physiology; D008875:Middle Aged; D009367:Neoplasm Staging; D019798:Neopterin / Q000652:urine*; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000652:urine; D012333:RNA, Messenger / Q000032:analysis
D050856:Interferon Regulatory Factor-1; D012333:RNA, Messenger; D019798:Neopterin; D007371:Interferon-gamma