PD17-12 SPATIAL MOLECULAR IMAGING IN SARCOMATOID RENAL CELL CARCINOMA REVEALS CROSSTALK BETWEEN IMMUNE CELLS AND TUMOR CELLS

Abstract

You have accessJournal of UrologyCME1 Apr 2023PD17-12 SPATIAL MOLECULAR IMAGING IN SARCOMATOID RENAL CELL CARCINOMA REVEALS CROSSTALK BETWEEN IMMUNE CELLS AND TUMOR CELLS Allison May, Claire Williams, Stephanie The, Sean Kim, Nathan Schurman, Greg Shelley, Tyler Robinson, Simpa Salami, Rohit Mehra, Aaron Udager, and Evan Keller Allison MayAllison May More articles by this author , Claire WilliamsClaire Williams More articles by this author , Stephanie TheStephanie The More articles by this author , Sean KimSean Kim More articles by this author , Nathan SchurmanNathan Schurman More articles by this author , Greg ShelleyGreg Shelley More articles by this author , Tyler RobinsonTyler Robinson More articles by this author , Simpa SalamiSimpa Salami More articles by this author , Rohit MehraRohit Mehra More articles by this author , Aaron UdagerAaron Udager More articles by this author , and Evan KellerEvan Keller More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003272.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Sarcomatoid renal cell carcinoma (sRCC) is thought to arise by epithelial to mesenchymal transition (EMT) of the parental tumor in diverse RCC including clear cell RCC (ccRCC). sRCC is also known to be highly immunomodulatory. Cells undergoing EMT and immune cells can have reciprocal feedback on each other; however, the role of such crosstalk in sRCC is unknown. Here, we evaluate the heterogeneity of EMT within sRCC in correlation with the immune microenvironment and explore mechanisms of crosstalk. METHODS: A sRCC nephrectomy specimen was subjected to single cell spatial transcriptomics of 1000 mRNA targets (NanoString CosMX). Semi-supervised clustering was performed and cell types were assigned by reference to scRNAseq data and then mapped spatially. Differential gene expression and cell to cell distance analysis was performed. In-vitro assays included treatment of 786-O and Caki-1 ccRCC lines with recombinant SPP1 and protein and mRNA analysis. RESULTS: Histopathologic evaluation revealed a ccRCC zone, a transition zone (tz) between the ccRCC and sRCC in which the ccRCC cells gained an increased mesenchymal morphology, and a well-developed sRCC zone. Transcriptomic data revealed four distinct tumor cell populations: a ccRCC, a tzRCC, and two sRCC populations. Importantly, a subset of the histologically-categorized ccRCC had a tzRCC transcriptional signature, demonstrating this signature is identifiable prior to development of morphologic features of sRCC (Figure 1c). CCL20, a promoter of macrophage recruitment, was highly expressed in tzRCC. Distance analysis showed macrophages were highly spatially correlated with tzRCC and sRCC cells. Macrophages near tzRCC differentially expressed SPP1. In-vitro treatment of ccRCC cells with recombinant SPP1 led to induction of EMT and further upregulation of CCL20 expression. CONCLUSIONS: We report a unique tumor cell population characterized by ccRCC morphology but harboring a transcriptome suggestive of progression towards sRCC. This provides rationale for the development of a novel molecular signature to subclassify ccRCC. We identified key genes, CCL20 and SPP1, that mediate crosstalk between RCC cells and macrophages that may serve as targets to inhibit progression to sRCC. Source of Funding: Clarke Family Fellowship for Kidney Cancer Research © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e500 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Allison May More articles by this author Claire Williams More articles by this author Stephanie The More articles by this author Sean Kim More articles by this author Nathan Schurman More articles by this author Greg Shelley More articles by this author Tyler Robinson More articles by this author Simpa Salami More articles by this author Rohit Mehra More articles by this author Aaron Udager More articles by this author Evan Keller More articles by this author Expand All Advertisement PDF downloadLoading ...