PD44-05 N-CADHERIN ANTAGONISTS N-Ac-CHAVC-NH2 RESCUE IMMUNOSUPPRESS CAUSED BY PD- L1/IDO-1 IN PROSTATE

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology II (PD44)1 Sep 2021PD44-05 N-CADHERIN ANTAGONISTS N-Ac-CHAVC-NH2 RESCUE IMMUNOSUPPRESS CAUSED BY PD- L1/IDO-1 IN PROSTATE Yi Sun, Jiaoti Huang, Qiang Wei, and Lu Yang Yi SunYi Sun More articles by this author , Jiaoti HuangJiaoti Huang More articles by this author , Qiang WeiQiang Wei More articles by this author , and Lu YangLu Yang More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002058.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Few prostate cancer patients benefit from current immunotherapies. We therefore aimed to explore new strategies to change this paradigm. METHODS: Human tissues, cell lines and in vivo experiments were used to determine whether and how N-cadherin impacts the production of PD-L1 and IDO-1. Then, we used PC3 bearing humanized nonobese diabetic/severe combined immunodeficiency IL2Rγnull (hNSG) mice with an intravenous injection of human CD34+ haematopoietic stem cells into the tail vein to test if the N-cadherin antagonists N-Ac-CHAVC-NH2 (designated ADH-1) could improve the therapeutic effect of tumour-infiltrating lymphocyte (TIL)-related treatment. RESULTS: N-cadherin dramatically upregulated the expression of PD-L1 and IDO-1 through IFN-g signalling, which could be reversed by N-cadherin knockout. In preclinical experiments, immune reconstitution obtained by TILs slowed tumour growth and extended survival time; however, this effect disappeared after immune system suppression by PD-L1 and IDO-1. Furthermore, ADH-1 effectively reduced the immunosuppression and enforced TIL-related therapy. CONCLUSIONS: These data show that the N-cadherin antagonist ADH-1 promotes TIL antitumour responses. This important hurdle must be overcome for tumours to generate a response to immunotherapy. Source of Funding: This study was supported by the National Natural Science Foundation of China (Grant No. 81370855, 81300627, 81702536, 81770756 and 81200551) for L.Y. and Q.W., This study was supported by the National key research and development program of China (Grant No. SQ2017YFSF090096) Q.W., the Prostate Cancer Foundation Young Investigator Award 2013, Foundation of Science &Technology Department of Sichuan Province (Grant No. 2015SZ0230, 2013SZ0006 and 2013SZ0093) for Q.W., Programs from Science and Technology Department of Sichuan Province (Grant No. 2018JY0089 and 2017HH0063) for Q.W., Young Investigator Award of Sichuan University 2017, and the Scientific Research Project of Health Department of Sichuan Province (No. 120203) for L.Y. Guangdong Basic and Applied Basic Research Foundation (2019A1515110125) for J.J. The National Natural Science Foundation of China (grant no. 81860454) for J.G. © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e738-e739 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yi Sun More articles by this author Jiaoti Huang More articles by this author Qiang Wei More articles by this author Lu Yang More articles by this author Expand All Advertisement Loading ...