You have accessJournal of UrologyBladder Cancer: Basic Research II1 Apr 2012891 VITAMIN D AND BCG IMMUNOTHERAPY Jong-Wei Hsu, Edward Messing, and Yi-Fen Lee Jong-Wei HsuJong-Wei Hsu Rochester, NY More articles by this author , Edward MessingEdward Messing Rochester, NY More articles by this author , and Yi-Fen LeeYi-Fen Lee Rochester, NY More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.986AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Bacillus Calmette-Guérin (BCG), a vaccine against tuberculosis (TB), has been used and proved to be one of the most effective treatments for superficial bladder cancer (BCa). However, the mechanisms of BCG action have not been completely understood, which limits the improvement of BCG therapy. Vitamin D deficiency has been associated with the high risk of TB infection, and the beneficial effect of UV exposure in TB patients was proven to be mediated via activation of vitamin D signals of innate immune cells. Thus, vitamin D signals might be involved in mediating BCG immunotherapy for BCa. METHODS We applied a transwell migration assay to examine vitamin D signal¡ߣs impact on the BCG-mediated innate immune cells¡ߣ migration. The corresponding pro-inflammatory cytokines induced by vitamin D/vitamin D receptor were screened by cytokine array and confirmed by ELISA. Preclinical evaluation of efficacy of intravesical BCG with 1£\,25-dihydroxyvitamin D3 (1,25-VD) therapy was performed using Nbutyl- N-(4-hydroxybutyl)-nitrosamine (BBN)-induced BCa mouse model. RESULTS ELISA assay revealed that treatment of BCa cells with 1,25-VD promotes BCG-induced interleukin 8 (IL-8) production, consequently inducing the migration of neutrophil-like cells, HL-60, and monocyte-like cells, THP-1. This 1,25-VD-mediated IL-8-induced innate immune cells migration was blocked by IL-8 neutralized antibody. These in vitro studies suggest that 1,25-VD could improve BCG responsiveness by enhancing recruitment of innate immune cells to promote cytotoxic killing of BCa cells. More importantly, our in vivo data revealed that intravesical treatment of 1,25-VD improves BCG efficacy where 1,25-VD+BCG treatment increased the survival rate of mice with BCa induced by BBN compared to BCG treatment alone. CONCLUSIONS The results of these studies indicate that 1,25-VD signaling is critical for success of BCG immunotherapy and co-treatment with 1,25-VD will enhance BCG's anti-tumor effects in BCa. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e362-e363 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jong-Wei Hsu Rochester, NY More articles by this author Edward Messing Rochester, NY More articles by this author Yi-Fen Lee Rochester, NY More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...