PD17-11 MOLECULAR PROFILING REVEALS IMMUNOSUPPRESSIVE TUMOR IMMUNE MICROENVIRONMENT IN PRIMARY VERSUS PAIRED ASYNCHRONOUS METASTATIC CLEAR CELL RENAL CELL CARCINOMA

Abstract

You have accessJournal of UrologyCME1 Apr 2023PD17-11 MOLECULAR PROFILING REVEALS IMMUNOSUPPRESSIVE TUMOR IMMUNE MICROENVIRONMENT IN PRIMARY VERSUS PAIRED ASYNCHRONOUS METASTATIC CLEAR CELL RENAL CELL CARCINOMA Brittney Cotta, Srinivas Nallandhighal, Daniel Triner, Nathan Graham, Rohit Mehra, Marcin Cieslik, Amy Kasputis, Todd Morgan, and Simpa Salami Brittney CottaBrittney Cotta More articles by this author , Srinivas NallandhighalSrinivas Nallandhighal More articles by this author , Daniel TrinerDaniel Triner More articles by this author , Nathan GrahamNathan Graham More articles by this author , Rohit MehraRohit Mehra More articles by this author , Marcin CieslikMarcin Cieslik More articles by this author , Amy KasputisAmy Kasputis More articles by this author , Todd MorganTodd Morgan More articles by this author , and Simpa SalamiSimpa Salami More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003272.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Clear cell renal cell carcinoma (ccRCC) is a highly immune infiltrated cancer, but how the tumor immune microenvironment (TIME) evolves during disease progression is unknown. Insights into heterogeneity within primary ccRCC raise questions about potential heterogeneity between primary and paired metastatic tumors. This information may improve understanding of immune evasion leading to metastatic disease and response to immunotherapy. In this study, we characterize and compare the TIME of primary ccRCC with paired asynchronous metastases. METHODS: Analysis of ccRCC patients who developed recurrence post radical nephrectomy and had both primary and metastatic tissue available. Whole-transcriptome sequencing was performed on formalin-fixed paraffin-embedded (FFPE) specimens using the illumina platform. Differential expression gene (DEG) analysis was performed using R package edgeR. Gene set enrichment analyses (GSEA) to identify hallmark pathway enrichment was performed using R package fgsea. TIME deconvolution was quantified using CIBEROSRT, an in silico flow cytometry tool. RESULTS: 42 tumor samples from 19 patients (19 primary tumors with 23 matched metastases) were analyzed. Metastasis sites included lung (n=6), bone (n=6), adrenal (n=4), liver (n=2), lymph node (n= 2), and soft tissue (n=3). Angiogenesis and epithelial to mesenchymal transition (EMT) were the most significantly enriched pathways in metastases compared to primary tumors (FDR < 5%). The primary tumors displayed a more immunosuppressive TIME than their matched metastases when comparing immune cell types. (Figure 1). The higher proportion of T regulatory cells (Tregs) in primary tumors was consistent compared against all metastasis tissue types. Metastasis samples displayed higher proportion of M2 macrophages (p=0.003), with the highest proportion in bone and soft tissue. Bone metastases also appeared to be more immunosuppressive in their TIME when compared to lung metastases, with greater Tregs and a lower immune content score. CONCLUSIONS: We demonstrate higher infiltration of immunosuppressive cells in the TIME of primary ccRCC compared with metastatic sites. Further studies are necessary to determine the prognostic and therapeutic significance of these findings. Source of Funding: None © 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 Brittney Cotta More articles by this author Srinivas Nallandhighal More articles by this author Daniel Triner More articles by this author Nathan Graham More articles by this author Rohit Mehra More articles by this author Marcin Cieslik More articles by this author Amy Kasputis More articles by this author Todd Morgan More articles by this author Simpa Salami More articles by this author Expand All Advertisement PDF downloadLoading ...