Mp10-03 Analyses of Tumor Microenvironment Changes of Clear Cell Renal Cell Carcinoma With Inferior Vena Cava Thrombus Following Neoadjuvant Anti-Pd-1 and Tyrosine Kinase Inhibitor Combination Therapy

You have accessJournal of UrologyKidney Cancer: Advanced (including Drug Therapy) I (MP10)1 May 2024MP10-03 ANALYSES OF TUMOR MICROENVIRONMENT CHANGES OF CLEAR CELL RENAL CELL CARCINOMA WITH INFERIOR VENA CAVA THROMBUS FOLLOWING NEOADJUVANT ANTI-PD-1 AND TYROSINE KINASE INHIBITOR COMBINATION THERAPY Yu Zhang, Min Lu, and LuLin Ma Yu ZhangYu Zhang , Min LuMin Lu , and LuLin MaLuLin Ma View All Author Informationhttps://doi.org/10.1097/01.JU.0001008588.39303.c9.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Immune checkpoint inhibitors (ICI) plus tyrosine kinase inhibitors (TKI) improves survival in patients with metastatic renal cell carcinoma (RCC). Nevertheless, the combination strategy has not been well studied preoperatively in RCC patients with inferior vena cava thrombus (IVCT). To evaluate the feasibility and safety of neoadjuvant ICI plus TKI combination therapy in RCC patients with IVCT and to explore the tumor microenvironment (TME) changes of both primary tumor (PT) and IVC thrombus. METHODS: A prospective cohort containing 10 patients with level II-IV IVC thrombus receiving neoadjuvant combination therapy was established since July 2022. All patients were given nephrectomy and thrombectomy after completing 3-cycle neoadjuvant therapy (200 mg pembrolizumab intravenously every 3 weeks plus 5 mg axitinib orally twice daily) according to the study scheme. We explored the combination therapy induced TME changes of both PT and IVCT through single-cell RNA sequencing (scRNA-seq) and multiplex immunohistochemistry (mIHC). RESULTS: Pathological responders had more infiltrating T cells and NK cells, while non-responders had more neutrophils and plasma cells. GSEA differential pathway analysis by TKI+ICB treatment non-responsive group and TKI+ICB treatment responsive group found that mitotic spindle, integrin signaling and phospholipid metabolism were up regulated in the non-responsive group. The responsive group up-regulated apoptosis, VEGF signaling, PD-1 signaling, chemokine signal axis, TCR signaling and B cell receptor signaling. We also found that IVCT significantly upregulated integrin signaling pathways than PT in the non-responsive group. The PT significantly up-regulated VEGF signaling and PD1 signaling axis in the responsive group. CONCLUSIONS: These findings provide insights into anti-PD-1 plus TKIs-regulated immune pathways in RCC with IVCT that should inform more effective therapeutic combinations that include T cell activators. Download PPTDownload PPTDownload PPTDownload PPT Source of Funding: None © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e137 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Yu Zhang More articles by this author Min Lu More articles by this author LuLin Ma More articles by this author Expand All Advertisement PDF downloadLoading ...