Pd16-04 Spatial Analysis of Primary and Metastatic Lesions in Sarcomatoid Renal Cell Carcinoma Reveals Insight to Tumor Biology and Immune Microenvironment

You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology I (PD16)1 May 2024PD16-04 SPATIAL ANALYSIS OF PRIMARY AND METASTATIC LESIONS IN SARCOMATOID RENAL CELL CARCINOMA REVEALS INSIGHT TO TUMOR BIOLOGY AND IMMUNE MICROENVIRONMENT Allison M. May, Claire Williams, Shaye Hagler, Michael McNiff, Tyler Robinson, Simpa Salami, Aaron Udager, and Evan T. Keller Allison M. MayAllison M. May , Claire WilliamsClaire Williams , Shaye HaglerShaye Hagler , Michael McNiffMichael McNiff , Tyler RobinsonTyler Robinson , Simpa SalamiSimpa Salami , Aaron UdagerAaron Udager , and Evan T. KellerEvan T. Keller View All Author Informationhttps://doi.org/10.1097/01.JU.0001009560.23593.56.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Sarcomatoid renal cell carcinoma (sRCC) is a dedifferentiation process that can occur in any kidney tumor, most commonly clear cell RCC (ccRCC). sRCC tumors have a high rate of metastasis. It is unknown whether metastatic lesions initiate from ccRCC or sRCC cells. Our prior work identified the ability to detect cells in a transition state from ccRCC to sRCC which was associated with dense macrophage and CD8 T-cell infiltrate. We hypothesized that clear cells in an early stage of transition to sRCC have more metastatic potential than fully mesenchymal sRCC cells. Here, we use spatial single cell transcriptomics and multiplex immunofluorescent staining to explore the tumor cell biology and corresponding immune microenvironment in matched primary and metastatic sRCC lesions. METHODS: Single cell spatial transcriptomics via NanoString's CosMx platform was performed on 6 specimens from two patients with matched primary and metastatic lesions. Fields of view were selected based on histology, selecting regions of ccRCC, "transition" (areas spatially between clear cell and sarcomatoid areas with an intermediate morphologic appearance), and sRCC. Unsupervised clustering was used to identify cell types which were mapped to spatial location. Immunoflourescent staining of 18 markers was performed on an adjacent cut of the same specimens and immune infiltrate was quantified via the Canopy CellScape platform. RESULTS: Unique tumor cell states were identified in ccRCC and sRCC areas. Transition areas were comprised largely of sRCC cell states with some component of ccRCC, consistent with prior findings. Metastatic lesions were comprised predominantly of ccRCC cell states with high expression of stemness genes such as POU5F1. Primary lesions had high T-cell infiltrate with the majority comprised of memory T-cells while metastatic lesions and much higher effector T-cell infiltrate. Ongoing work includes spatial analysis of tumor cell/immune interactions. CONCLUSIONS: These findings support the hypothesis that initial metastases in sRCC arise from clear cell RCC cells with stem-like properties, which may then progress to develop sarcomatoid features. The immune microenvironment varies from primary to metastatic lesions with a higher density of effector T-cells in metastases. Further exploration of these findings will have important implications for understanding sRCC biology and response to immunotherapy in primary versus metastatic lesions. Source of Funding: Clark Family Kidney Cancer Research FellowshipNCI/NIH T32 Research Fellow, Division of Urologic Oncology at University of MichiganRogel Cancer Center Forbes Institute for Cancer Discovery Scholarship © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e366 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Allison M. May More articles by this author Claire Williams More articles by this author Shaye Hagler More articles by this author Michael McNiff More articles by this author Tyler Robinson More articles by this author Simpa Salami More articles by this author Aaron Udager More articles by this author Evan T. Keller More articles by this author Expand All Advertisement PDF downloadLoading ...