MP01-20 TLR7/8-AGONIST-LOADED M1-MACROPHAGE-DERIVED NANOVESICLES PROMOTE THE POLARIZATION OF MACROPHAGES TO ENHANCE BLADDER CANCER IMMUNOTHERAPY

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology I (MP01)1 Apr 2020MP01-20 TLR7/8-AGONIST-LOADED M1-MACROPHAGE-DERIVED NANOVESICLES PROMOTE THE POLARIZATION OF MACROPHAGES TO ENHANCE BLADDER CANCER IMMUNOTHERAPY Qing Zhang*, Wenmin Cao, Wenfeng Lu, Yuanzhen Ding, and Hongqian Guo Qing Zhang*Qing Zhang* More articles by this author , Wenmin CaoWenmin Cao More articles by this author , Wenfeng LuWenfeng Lu More articles by this author , Yuanzhen DingYuanzhen Ding More articles by this author , and Hongqian GuoHongqian Guo More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000815.020AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Tumor-associated macrophages (TAM) are abundant in many cancers including bladder cancer, and often display an immune-suppressive M2-like phenotype to fosters tumor growth, evade immune cell attacks and promotes resistance to therapy. Immunotherapy like PD-1/PD-L1 antibody modulates TEM immune cells to attacks bladder cancer cells since the first approval of atezolizumab in May 2016. However, the immune checkpoint inhibitor therapy may be hampered by M2 TAMs. In this study, we used exosome-mimetic nanovesicles derived from M1 macrophages and loaded with TLR7/8-agonist R848 which is a potent driver of the M1 phenotype (M1NV-R848), to repolarize M2 to M1 macrophages, and investigated whether the macrophage repolarization can potentiate the anticancer efficacy of aPD-1 in bladder cancer. METHODS: M1NVs were obtained from LPS-treated RAW264.7 cells (M1 macrophages) by serial extrusion through polycarbonate membranes with different pore sizes, then R848 was loaded. Cellular uptake, cytotoxicity and treatment effect of M1NV-R848 with or without PD-1 were performed in vitro and in vivo. Western blot, RT-qPCR, IF and IHC were performed to detect the expression of protein and mRNA of macrophages marker. RESULTS: M1NV-R848 treatment induced successful polarization of M2 macrophages to M1 macrophages in vitro and in vivo, compared with M1NV or R848 alone. Intravenous injection of M1NV-R848 into bladder cancer MB49 tumor-bearing mice suppressed tumor growth and metastasis to lung. Importantly, injection of a combination of M1NV-R848 and aPD-1 to mouse further reduced the tumor size and lung metastasis, compared to the injection of either M1NV-R848 or aPD-1 alone. CONCLUSIONS: Thus, our study indicates that M1NV-R848 injection can repolarize M2 TAMs to M1 macrophages and potentiate antitumor efficacy of the PD-1 checkpoint inhibitor therapy in bladder cancer. Source of Funding: This study was funded by the National Natural Science Foundation of China (81802535), China postdoctoral fund(223427), Nanjing Medical Science and technique Development Foundation (YKK 18064) © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e10-e10 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Qing Zhang* More articles by this author Wenmin Cao More articles by this author Wenfeng Lu More articles by this author Yuanzhen Ding More articles by this author Hongqian Guo More articles by this author Expand All Advertisement PDF downloadLoading ...