LBA02-05 DEFINING INNATE IMMUNE MEMORY IN THE MECHANISM OF BCG IMMUNOTHERAPY FOR BLADDER CANCER

Abstract

You have accessJournal of UrologyCME1 Apr 2023LBA02-05 DEFINING INNATE IMMUNE MEMORY IN THE MECHANISM OF BCG IMMUNOTHERAPY FOR BLADDER CANCER Song Jiang, Gil Redelman-Sidi, Eugene J. Pietzak, Bernard H. Bochner, and Michael Glickman Song JiangSong Jiang More articles by this author , Gil Redelman-SidiGil Redelman-Sidi More articles by this author , Eugene J. PietzakEugene J. Pietzak More articles by this author , Bernard H. BochnerBernard H. Bochner More articles by this author , and Michael GlickmanMichael Glickman More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003361.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Intravesical instillation of the live attenuated mycobacterium Bacillus Calmette-Guerin (BCG) remains the most effective therapy for the treatment of non-muscle invasive bladder cancer. An increasing body of evidence suggests that the innate immune system has characteristics that involve a heterologous memory of past insults through a process thought to involve epigenetic reprogramming, termed trained immunity. We seek to investigate the potential for innate immune training as a predictor of the anti-tumor effects of BCG. METHODS: A prospective biospecimen collection was performed on venous blood from non-muscle invasive bladder cancer patients prior to receiving intravesical BCG therapy. An ex vivo training protocol was performed on peripheral blood monocytes as previously described. Subsequently, cells were stimulated with 25 ng/ml lipopolysaccharide (a TLR4 agonist) for 24 hours. Cell free supernatant was measured for TNF-alpha production by enzyme-linked immunosorbent assay. RESULTS: In vitro training of primary monocytes induced an increase in proinflammatory cytokine production upon re-stimulation. In our in vitro training experiments, there was demonstrable interpatient variability seen pre-BCG exposure in a cohort of 30 NMIBC patients (Figure 1). Kaplan Meier analysis of this NMIBC patient cohort demonstrated improved recurrence free survival in individuals with a higher innate immune memory response. CONCLUSIONS: We present data on a trained innate immune phenotype on primary monocytes collected from patient samples. We found that innate immune training correlated improved recurrence free survival in NMIBC patients treated with BCG. Such insight will have potential clinical impact on the development of biomarkers and clinical assays that could predict immune responsiveness to BCG a priori, as well as identify possible immunological adjuvants that could enhance the effect of intravesical BCG. Source of Funding: ASCO YIANCI SPORE in Bladder Cancer © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1188 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Song Jiang More articles by this author Gil Redelman-Sidi More articles by this author Eugene J. Pietzak More articles by this author Bernard H. Bochner More articles by this author Michael Glickman More articles by this author Expand All Advertisement PDF downloadLoading ...