Event Abstract Back to Event Polyomavirus BK large tumor antigen exerts tolerogenic signatures with immunodominant p53-binding regions in prostate cancer Maurizio Provenzano1* 1 Division of Urology, University Hospital of Zurich, Oncology Unit, Switzerland Polyomavirus BK (BKV) large tumor antigen (L-Tag) has been recently identified as a potential co-factor in the development of prostate cancer (PCa) but its role as target of immune responses in this malignancy remains unexplored. A regulatory profiling elicited by L-Tag peptide-pool stimulation has been observed in BKV seropositive PCa patients bearing BKV positive lesions and evidence of biochemical recurrence. Differently, T cells against p53-binding regions of L-Tag exquisitely belong to effector/memory CD8+ T cells populations in BKV seropositive healthy donors. The ambiguous activity of L-Tag prompted us to investigate the role of functional regions within L-Tag in eliciting peculiar immune responses in PCa. Two peptides, L-Tag406-414 and L-Tag579-587, nested in the p53-binding regions of L-Tag and previously documented to induce pro-inflammatory responses in healthy donors, triggered an immune regulatory response (IL-10- and TGF-β-producing CD4+CD25+CD127- T cells) with suppressive properties in 61% and 54% of PCa patients studied (n=20), respectively. In contrast, four peptides identified within L-Tag regions non specifically required for virus-induced malignant transformation, recalled IFN-γ-producing effector/memory CD8+ and CD4+ T cells with cytotoxic (CD107+) and no-exhausted (PD-1-) phenotype, able to boost immunogenic activities in PCa patients with a BKV-driven tolerogenic signatures. These findings suggest that strategic regions of L-Tag appointed to carry out oncogenic activities might orchestrate tumor-promoting environment. However, it also gives evidence that a systemic boosting of BKV seropositive PCa patients with immunogenic portions of BKV L-Tag would generate potent antigen-specific immune responses and thereby break the tolerogenic potential governed by BKV L-Tag in this disease. References G. Sais, S. Wyler, T. Hudolin, I. Banzola, C. Mengus, L. Bubendorf, P. J. Wild, H. H. Hirsch, T. Sulser, G. C. Spagnoli and M. Provenzano: Differential patterns of large tumor antigen-specific immune responsiveness in patients with BK polyomavirus-positive prostate cancer or benign prostatic hyperplasia. J Virol, 86(16), 8461-71 (2012) M. Provenzano, L. Bracci, S. Wyler, T. Hudolin, G. Sais, R. Gosert, P. Zajac, G. Palu, M. Heberer, H. H. Hirsch and G. C. Spagnoli: Characterization of highly frequent epitope-specific CD45RA+/CCR7+/- T lymphocyte responses against p53-binding domains of the human polyomavirus BK large tumor antigen in HLA-A*0201+ BKV-seropositive donors. J Transl Med, 4, 47 (2006) Keywords: virus-induced oncogenesis, breaking immunological tolerance, regulatory T cells, prostate cancer, polyomavirus BK Large tumor antigen Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Host-pathogen interactions Citation: Provenzano M (2013). Polyomavirus BK large tumor antigen exerts tolerogenic signatures with immunodominant p53-binding regions in prostate cancer. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00055 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 08 Mar 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Maurizio Provenzano, Division of Urology, University Hospital of Zurich, Oncology Unit, Zurich, Zurich, 8091, Switzerland, maurizio.provenzano@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Maurizio Provenzano Google Maurizio Provenzano Google Scholar Maurizio Provenzano PubMed Maurizio Provenzano Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.