Abstract
RESULTS: IL-18Bpa was expressed and secreted by the prostate cancer cell lines DU145 and PC3, but not by LNCaP and CWR22, upon interferon(IFN) stimulation. IFN-induced secretion of IL-18Bpa was enhanced by added TNF, IFNand IFN. The IL-18Bpa secreted from DU145 and PC3 functionally inhibited IL-18. Conditioned medium from IL-18Bpa-overexpressed PC3 cells suppressed CD8+ IFN+ cells and CD4+ cells and appeared to decrease TH1 cells in human peripheral blood cultures. Immunohistochemical analyses showed positive IL18Bpa staining in prostate cancer cells as well as in macrophages in radical prostatectomy specimens. Significant differences in post-DRE urinary IL-18Bpa levels (normalized by total protein) were found between cases with and without cancer on biopsy (P = 0.02) and serum IL-18Bpa levels correlated with Gleason score (P = 0.03). CONCLUSIONS: Our finding of elevated IL-18Bpa secretion from prostate cancer cells suggests an attempt by cancer to escape immune surveillance. IL-18Bpa merits further study as a marker of aggressive prostate cancer and as a therapeutic target.
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