Mp10-01 Cd73 Blockade Potentiates Fh-Cgas-Sting Axis in the Microenvironment of Renal Cell Carcinoma

You have accessJournal of UrologyKidney Cancer: Advanced (including Drug Therapy) I (MP10)1 May 2024MP10-01 CD73 BLOCKADE POTENTIATES FH-CGAS-STING AXIS IN THE MICROENVIRONMENT OF RENAL CELL CARCINOMA Yongmei Chen, Yuanyuan Bai, Daoxun Chen, Dongming Lu, Yingming Sun, and Yongyang Wu Yongmei ChenYongmei Chen , Yuanyuan BaiYuanyuan Bai , Daoxun ChenDaoxun Chen , Dongming LuDongming Lu , Yingming SunYingming Sun , and Yongyang WuYongyang Wu View All Author Informationhttps://doi.org/10.1097/01.JU.0001008588.39303.c9.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: This study aims to investigate a new renal cell carcinoma (RCC) treatment strategy by targeting tumor metabolism via CD73 blockade and validate its safety and effectiveness. METHODS: We analyzed CD73-related bioinformatics data from the TCGA database and GEO database. In vitro and in vivo was used to evaluate the safety and efficacy of CD73 blockade. We applied transcription sequencing, and protein chip analysis to figure out the pathway involved. FH-cGAS-STING pathway was validated by flowcytometry, WB, and immunohistochemistry. RESULTS: The TCGA database showed that CD73 expression was higher in KIRC (clear cell renal cell carcinoma) and associate with poor prognosis. Functional enrichment analysis suggested hypoxia and energy metabolism pathways may promote. In vitro and in vivo indicated the anti-tumor effect and safety under CD73 blockade exposure. Tumor protein chip analysis showed that inhibiting CD73 could significantly increase IFN secretion. Metabolic and transcription sequencing results showed that CD73 was associated with fumaric acid metabolism and may regulate IFN secretion through a cGAS/STING-dependent manner. Flow cytometry results showed that inhibiting CD73 could delete M2 macrophages. Virtual molecular docking and WB results showed that CD73 blockade attenuated FH activity, and accumulated fumaric acid in RCC cells, which subsequently activated cGAS-STING pathway. CONCLUSIONS: CD73 blockade is an effective and safe strategy by targeting tumor metabolism, and potential to launch clinical trial of anti-RCC. Download PPTDownload PPTDownload PPTDownload PPT Source of Funding: The Scientific Fund of Sanming Science and Technology Bureau (2022-S-71) © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e136 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Yongmei Chen More articles by this author Yuanyuan Bai More articles by this author Daoxun Chen More articles by this author Dongming Lu More articles by this author Yingming Sun More articles by this author Yongyang Wu More articles by this author Expand All Advertisement PDF downloadLoading ...