Immunomodulatory IL‐18 binding protein is produced by prostate cancer cells and its levels in urine and serum correlate with tumor status

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Abstract
Cytokines may play a role in the initiation and progression of prostate cancer. A cytokine antibody array was previously applied to prostatic fluid obtained from patients with prostate cancer, and interleukin 18 binding protein (IL‐18BP), a potent inhibitor of interleukin 18, was noted to be significantly upregulated in cases with large volume disease. We sought to further characterize the association of IL‐18BP with prostate cancer and determine whether IL‐18BP levels in patient serum and urine samples had clinical relevance. IL‐18BP was expressed and secreted by the prostate cancer cell lines DU145 and PC3 but not by LNCaP and CWR22, upon interferon‐γ (IFN‐γ) stimulation. IFN‐γ‐induced secretion of IL‐18BP was enhanced by added TNF‐α, IFN‐α and IFN‐β. The IL‐18BP secreted from DU145 and PC3 functionally inhibited IL‐18. Immunohistochemical analyses showed positive IL‐18BP staining in prostate cancer cells as well as in macrophages in radical prostatectomy specimens. Significant differences in urinary IL‐18BP levels (normalized by total protein) collected post‐DRE were found between cases with and without cancer on biopsy (p = 0.02) and serum IL‐18BP levels correlated with Gleason score (p = 0.03). Our finding of elevated IL‐18BP secretion from prostate cancer cells suggests an attempt by cancer to escape immune surveillance. IL‐18BP merits further study as a marker of aggressive prostate cancer and as a therapeutic target.

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