MP04-17 ALTERATIONS IN RNASET2 FACILITATE A PRO TUMOR MICROENVIRONMENT ASSOCIATED WITH WORSE CLINICAL OUTCOMES IN CLEAR CELL RCC

Abstract

You have accessJournal of UrologyCME1 Apr 2023MP04-17 ALTERATIONS IN RNASET2 FACILITATE A PRO TUMOR MICROENVIRONMENT ASSOCIATED WITH WORSE CLINICAL OUTCOMES IN CLEAR CELL RCC Taylor Peak, Andrew Chang, Nick Chakiryan, Joseph Johnson, Anders Berglund, Doug Marchion, Asmaa Elkenawi, Noel Clark, Natasha Francis, Paola Ramos Echevarria, Nusheen Immen, Jasreman Dhillon, James Mule, Liang Wang, and Brandon Manley Taylor PeakTaylor Peak More articles by this author , Andrew ChangAndrew Chang More articles by this author , Nick ChakiryanNick Chakiryan More articles by this author , Joseph JohnsonJoseph Johnson More articles by this author , Anders BerglundAnders Berglund More articles by this author , Doug MarchionDoug Marchion More articles by this author , Asmaa ElkenawiAsmaa Elkenawi More articles by this author , Noel ClarkNoel Clark More articles by this author , Natasha FrancisNatasha Francis More articles by this author , Paola Ramos EchevarriaPaola Ramos Echevarria More articles by this author , Nusheen ImmenNusheen Immen More articles by this author , Jasreman DhillonJasreman Dhillon More articles by this author , James MuleJames Mule More articles by this author , Liang WangLiang Wang More articles by this author , and Brandon ManleyBrandon Manley More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003215.17AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: M2 macrophage polarization (CD163) leads to T cell exhaustion and worse clinical outcomes in ccRCC patients. Recently, our group has identified a novel splice variant of RNASET2, a protein normally contributing to anti-tumor activity. This splice variant was associated with worse clinical outcomes in ccRCC patients. We set out to determine the expression patterns for M2 macrophages and RNASET2, and their relationship with the RNASET2 splice variant. We hypothesize that the splice variant leads to abnormal protein formation, allowing for a tumor microenvironment that favors growth. METHODS: We obtained primary tumor samples from 75 patients with ccRCC. Tissue sections from these specimens were obtained from the tumor core, tumor edge, and stroma (Figure 1). IHC was performed, staining for RNASET2, M2 macrophage (CD 163), and markers for T cell exhaustion (TIM3, CD8). In addition, RNA sequencing data was utilized to identify the RNASET2 splice variant expression in all tumors. Expression patterns of these cellular markers were analyzed, and then stratified based on whether the tumor was splice variant positive (SV+) or splice variant negative (SV-) RESULTS: Expression of CD163 was inversely correlated with expression of RNASET2 in the tumor core and tumor edge (Figure 2). Interestingly, SV+ tumors had overall higher RNASET2 expression. However, when relative extracellular to intracellular RNASET2 staining was compared, the SV- tumors possessed relatively higher extracellular expression. Finally, when evaluating expression as a prognostic indicator, we found that high co-expression of CD163 and RNASET2 led to worse overall survival relative to low co-expression. This was seen in the tumor (47 vs 138 mo, p<0.001), tumor edge (80 vs 174 mo, p=0.001) and stroma (15 vs 125 mo, p<0.001). CONCLUSIONS: This data represents the first evidence that a relationship exists between M2 macrophages and RNASET2 in kidney cancer. We have demonstrated through staining of patient tissue samples that high RNASET2 expression is correlated with low M2 polarization of macrophages, and vice versa. Furthermore, based on relative extracellular localization, SV- tumors are more effective at secreting RNASET2 to promote anti-tumor effect. Source of Funding: N/A © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e40 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Taylor Peak More articles by this author Andrew Chang More articles by this author Nick Chakiryan More articles by this author Joseph Johnson More articles by this author Anders Berglund More articles by this author Doug Marchion More articles by this author Asmaa Elkenawi More articles by this author Noel Clark More articles by this author Natasha Francis More articles by this author Paola Ramos Echevarria More articles by this author Nusheen Immen More articles by this author Jasreman Dhillon More articles by this author James Mule More articles by this author Liang Wang More articles by this author Brandon Manley More articles by this author Expand All Advertisement PDF downloadLoading ...