892 PRELIMINARY RESULTS OF PERIOPERATIVE OUTCOMES AND ONOCOLIGIC EFFICACY FROM A SINGLE INSTITUTION RANDOMIZED CONTROLLED TRIAL OF OPEN VERSUS ROBOTIC ASSISTED RADICAL CYSTECTOMY

Abstract

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 signalis impact on the BCG-mediated innate immune cellsi 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 NbutylN-(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.