PD17-04 THE ROLE OF CYTOREDUCTIVE NEPHRECTOMY WITH IMMUNE CHECKPOINT INHIBITOR THERAPIES IN METASTATIC RENAL CELL CARCINOMA MURINE MODEL

Abstract

You have accessJournal of UrologyCME1 Apr 2023PD17-04 THE ROLE OF CYTOREDUCTIVE NEPHRECTOMY WITH IMMUNE CHECKPOINT INHIBITOR THERAPIES IN METASTATIC RENAL CELL CARCINOMA MURINE MODEL Jee Soo Park, Myung Eun Lee, Won Sik Jang, Jongchan Kim, Se Mi Park, and Won Sik Ham Jee Soo ParkJee Soo Park More articles by this author , Myung Eun LeeMyung Eun Lee More articles by this author , Won Sik JangWon Sik Jang More articles by this author , Jongchan KimJongchan Kim More articles by this author , Se Mi ParkSe Mi Park More articles by this author , and Won Sik HamWon Sik Ham More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003272.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Since CARMENA trial found non-inferiority of sunitinib alone, the contemporary role of cytoreductive nephrectomy (CN) has been significantly downsized. However, updated CARMENA trial results demonstrated certain subsets with metastatic renal cell carcinoma (mRCC) may still benefit from CN. We tried to assess the role of CN in combination with immune checkpoint inhibitor (ICI) from the perspective tumor immune microenvironment (TIME). METHODS: Low- and high-tumor burden pulmonary metastatic orthotopic murine mRCC models have been developed. Anti-PD-1 and anti-CTLA-4 antibodies were systemically injected through the peritoneum every 3 days. Renca implanted kidney was removed in the CN performed group. For the upfront CN plus ICI group, CN was performed 1 day before the ICI, while CN was performed 5 days after ICI for the deferred CN plus ICI group. The remodeling of the TIME was determined using immunofluorescence analysis. RESULTS: Low- and high-tumor burden murine mRCC models have been successfully developed with statistically significant difference in median survival (p<0.05). In low-tumor burden model (Figure 1A), upfront CN plus ICI group demonstrated significantly better survival outcomes compared to deferred CN plus ICI group. In high-tumor burden model (Figure 1B), similar results were shown as low-tumor burden model, except no significant survival difference between ICI only and CN only group, and between upfront CN plus ICI and deferred CN plus ICI group. Immunofluorescence analysis demonstrated that CN modulate TIME by increasing M1 tumor-associated macrophage (TAM) and at the same time decreasing M2 TAM (Figure 2). CONCLUSIONS: This study is the first animal study to demonstrate the role of CN in combination with ICI. We have shown that the CN has certain role in the immune-oncology (IO) era and was associated with improved survival by the regulation of M1 and M2 TAM. CN also regulated myeloid-derived suppressor cells and regulatory T cells in combination with ICIs although not to be significant in our study. Source of Funding: This work was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute funded by the Ministry of Health & Welfare, Republic of Korea [grant number: HI17C1095], and the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) [grant number: 2019R1A2C1002863 and 2022R1A2C2003831] © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e496 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jee Soo Park More articles by this author Myung Eun Lee More articles by this author Won Sik Jang More articles by this author Jongchan Kim More articles by this author Se Mi Park More articles by this author Won Sik Ham More articles by this author Expand All Advertisement PDF downloadLoading ...