MP16-12 METHYLATION CAN REGULATE THE EXPRESSION OF PD-L1 IN SMALL CELL PROSTATE CANCER

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology I (MP16)1 Apr 2020MP16-12 METHYLATION CAN REGULATE THE EXPRESSION OF PD-L1 IN SMALL CELL PROSTATE CANCER Yi Sun*, Qiang Wei, Jiaoti Huang, and Lu Yang Yi Sun*Yi Sun* More articles by this author , Qiang WeiQiang Wei More articles by this author , Jiaoti HuangJiaoti Huang More articles by this author , and Lu YangLu Yang More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000841.012AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: As a broad generality, programmed death-ligand 1 (PD-L1)–positive tumors tend to have a higher rate of objective response to PD-1/PD-L1 blockade, and PD-L1 expression remains an important clinically validated predictive biomarker for response, in addition, according to some published paper, the expression of PD-L1 is much higher in small cells neuroendocrine prostate cancer. So we focus on the mechanism of this phenomena. METHODS: We collect the human tissue samples and performed the Immunohistochemistry (IHC) stain to test the expression of PD-L1, and also use the Interferon-g (IFN-g) to treat some cells lines test the expression of PD-L1. Moreover, we also test the expression of PD-L1 in xenograft mice model treated by IFN-g. And then we test the expression and the activation of the whole IFN respond pass-way in human tissue samples, mice tumor samples and cell lines. To test the effect of JAK/STAT pass-way on this process, we block the JAK/STAT pass-way and then test the IFN respond again. And then we test the impact of methylation on the expression of JAK1 also the INF respond. RESULTS: The comprehensive evaluation of PD-L1 expression in prostate cancer showed that PD-L1 expression is rare in primary prostate cancers, but increased rates of PD-L1 positivity were observed in Small Cell Neuroendocrine (SCNE) prostate cancer. Similar results could be found in Small Cell Neuroendocrine Cancer (SCNC) cells and the SCNC mice model under the stimulation of IFN-g. Block the JAK1/STAT1 pass-way could drastically inhibit this process. The expression of JAK1 and this whole process also suppressed by demethylation. CONCLUSIONS: This study demonstrated that PD-L1 expression is much higher in a small cell prostate cancer. And the reason behind this phenomenon is the JAK/STAT pass-way regulated by methylation. Source of Funding: This study was supported by the National Natural Science Foundation of China (Grant No. 81370855, 81300627, 81702536, 81770756 and 81200551), This study was supported by the National key research and development program of China (Grant No. SQ2017YFSF090096), the Prostate Cancer Foundation Young Investigator Award 2013, Foundation of Science &Technology Department of Sichuan Province (Grant No. 2015SZ0230, 2013SZ0006 and 2013SZ0093), Programs from Science and Technology Department of Sichuan Province (Grant No. 2018JY0089 and 2017HH0063), Young Investigator Award of Sichuan University 2017, and the Scientific Research Project of Health Department of Sichuan Province (No. 120203). © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e219-e220 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yi Sun* More articles by this author Qiang Wei More articles by this author Jiaoti Huang More articles by this author Lu Yang More articles by this author Expand All Advertisement PDF downloadLoading ...