Abstract

The role of the polyomavirus BK (BKV) large tumor antigen (L-Tag) as target of immune response in patients with prostate cancer (PCa) has not been investigated so far. In this study we have comparatively analyzed humoral and cellular L-Tag specific responsiveness in age matched patients bearing PCa or benign prostatic hyperplasia (BPH), expressing or not expressing BKV L-Tag specific sequences in their tissue specimens, and in non-age-matched healthy individuals. Furthermore, results from patients with PCa were correlated to 5-year follow-up clinical data focusing on evidence of biochemical recurrence (BR) following surgery (PSA≥0.2ng/ml).In peripheral blood mononuclear cells (PBMC) from patients with PCa with evidence of BR and BKV L-Tag positive tumors, stimulation with peptides derived from BKV L-Tag, but not those derived from Epstein Barr virus, influenza virus or Cytomegalovirus, induced a peculiar cytokine gene expression profile, characterized by high expression of IL-10 and TGFβ-1 and a low expression of IFN-γ genes. This pattern was confirmed by protein secretion data and correlated with high levels of anti BKV L-Tag IgG. Furthermore, in PBMC from these PCa bearing patients, L-Tag derived peptides significantly expanded an IL-10-secreting CD4(+)CD25(+(high))CD127(-(dim))FoxP3(+) T cell population with an effector memory phenotype (CD103(+)) capable of inhibiting proliferation of autologous anti-CD3/CD28 triggered CD4(+)CD25(-) T cells. Collectively, our findings indicate that potentially tolerogenic features of L-Tag specific immune response are significantly associated with tumor progression in patients with BKV+ PCa.