MP47-16 PRETREATMENT PERIPHERAL BLOOD MONOCYTE SUBSET SIGNATURE IN STAGE IV RENAL CELL CARCINOMA PATIENTS PREDICTS OUTCOME TO DENDRITIC CELL VACCINATION (2015)

You have accessJournal of UrologyKidney Cancer: Basic Research II1 Apr 2015MP47-16 PRETREATMENT PERIPHERAL BLOOD MONOCYTE SUBSET SIGNATURE IN STAGE IV RENAL CELL CARCINOMA PATIENTS PREDICTS OUTCOME TO DENDRITIC CELL VACCINATION Jason Muhitch, Alexander Wald, Mohammad Habiby Kermany, Joseph Tario, Anand Sharda, Marc Ernstoff, and Thomas Schwaab Jason MuhitchJason Muhitch More articles by this author , Alexander WaldAlexander Wald More articles by this author , Mohammad Habiby KermanyMohammad Habiby Kermany More articles by this author , Joseph TarioJoseph Tario More articles by this author , Anand ShardaAnand Sharda More articles by this author , Marc ErnstoffMarc Ernstoff More articles by this author , and Thomas SchwaabThomas Schwaab More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1536AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Clinical trials have demonstrated that dendritic cell (DC) vaccination can initiate durable anti-tumor immunity in a subset of cancer patients resulting in complete responses, even in stage IV Renal Cell Carcinoma (RCC). In many DC vaccination approaches, peripheral blood monocytes serve as precursors to generate DC. Circulating monocytes consist of three distinct subsets (CD14+, CD16- classical, CD14+, CD16+ intermediate, and CD14dim, CD16+ non-classical). Very little information is available regarding the fate of these subsets upon differentiation into DC. Moreover, the status of intermediate and non-classical monocytes in cancer patients has not been formally investigated. The goal of this study was to investigate whether the composition of pre-treatment, circulating monocyte subsets can predict patient outcome to DC vaccination and if DC derived from non-classical monocytes are superior antigen presenting cells. METHODS Pretreatment peripheral blood monocytes from 13 patients who received DC vaccination in a phase I clinical trial were obtained and subsets were identified by CD14 and CD16 expression. Monocytes subsets were isolated from healthy donors, cultured into DC, and analyzed for costimulatory molecule by flow cytometry. RESULTS Stage IV RCC patients exhibiting complete responses to vaccination exhibited a unique monocyte subset signature in pretreatment peripheral blood with approximately twice as many non-classical monocytes (17.6 ± 0.4, mean ± SD) compared to partial responders (7.5% ± 3.1, P < 0.01 respectively), patients with progressive disease(4.8% ± 4.1, P < 0.05), or healthy donors (7.7% ± 2.8, P < 0.01). Peripheral blood from complete responders contained decreased percentages of classical monocytes (62.5% ± 1.0, P < 0.05 vs. all groups) compared to partial responders (85.4% ± 3.9), progressive disease (84.7% ± 8.9), and healthy controls (84.7% ± 3.6). When non-classical monocytes were cultured into DC, these populations had elevated percent positive values for costimulatory molecules CD80 (96%), CD86 (91%), and HLA-DR (99%) compared to classical monocyte-derived DC (65%, 54%, 60%, respectively), suggesting that DC derived from non-classical monocytes are superior antigen presenting cells. CONCLUSIONS These findings demonstrate that monocyte subsets in peripheral blood may be an important prognostic tool prior to DC vaccination. Future studies will evaluate whether enrichment of non-classical populations prior to culture into DC can improve T cell activation. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e557-e558 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jason Muhitch More articles by this author Alexander Wald More articles by this author Mohammad Habiby Kermany More articles by this author Joseph Tario More articles by this author Anand Sharda More articles by this author Marc Ernstoff More articles by this author Thomas Schwaab More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...