Differential patterns of large tumor antigen-specific immune responsiveness in patients with BK polyomavirus-positive prostate cancer or benign prostatic hyperplasia.

Abstract

The role of the polyomavirus BK (BKV) large tumor antigen (L-Tag) as a target of immune response in patients with prostate cancer (PCa) has not been investigated thus far. In this study, we comparatively analyzed humoral and cellular L-Tag-specific responsiveness in age-matched patients bearing PCa or benign prostatic hyperplasia, 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) after surgery (prostate specific antigen level of ≥0.2 ng/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 the 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 interleukin-10 (IL-10) and transforming growth factor β1 and low expression of gamma interferon 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(-) 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.

• Authors: Giovanni Sais, Stephen Wyler, Tvrtko Hudolin, Irina Banzola, Chantal Mengus, Lukas Bubendorf, Peter J Wild, Hans H Hirsch, Tullio Sulser, Giulio C Spagnoli, Maurizio Provenzano
• Journal: Journal of virology (J Virol) Vol. 86 Issue 16 Pg. 8461-71 (Aug 2012) ISSN: 1098-5514 [Electronic] United States
• PMID: 22647697 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Viral
• Antigens, Neoplasm
• Cytokines
• Viral Proteins

Topics

• Aged
• Aged, 80 and over
• Antibodies, Viral (blood)
• Antigens, Neoplasm (immunology)
• BK Virus (immunology)
• Cytokines (biosynthesis, metabolism)
• Humans
• Immunologic Memory
• Leukocytes, Mononuclear (immunology)
• Lymphocyte Subsets (immunology)
• Male
• Middle Aged
• Prostatic Hyperplasia (immunology, pathology, virology)
• Prostatic Neoplasms (immunology, pathology, virology)
• Viral Proteins (immunology)