Mp22-14 lag3 expression associated with survival in patients with bladder cancer

You have accessJournal of UrologyCME1 Apr 2023MP22-14 LAG3 EXPRESSION ASSOCIATED WITH SURVIVAL IN PATIENTS WITH BLADDER CANCER Tamir Sholklapper, Laura Bukavina, Andres Correa, Alexander Kutikov, and Philip Abbosh Tamir SholklapperTamir Sholklapper More articles by this author , Laura BukavinaLaura Bukavina More articles by this author , Andres CorreaAndres Correa More articles by this author , Alexander KutikovAlexander Kutikov More articles by this author , and Philip AbboshPhilip Abbosh More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003247.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Expression of lymphocyte activation gene-3 (LAG3), an immune cell transmembrane protein with a regulatory impact on tumor microenvironments, has been identified as a promising checkpoint for emerging immunotherapies. We sought to evaluate the impact of LAG3 expression on bladder cancer survival and the immune regulatory environment. (Figure 1A) METHODS: RNA seq data for bladder cancer was obtained in TCGA from TCGA Data Portal (https://tcga-data.nci.nih.gov/docs/publications/tcga/). Wilcoxon rank-sum test was used for all pairwise comparisons. Spearman Rho was used for all correlations, and P-values were calculated using either the exact permutation distributions (for small sample sizes) or large-sample approximations. All P-values are from two-sided tests, and P < .05 was used as the threshold for statistical significance. The Kaplan-Meier method and log-rank test were used to evaluate overall survival and compare inter-group survival, respectively. Sub-analyses were performed to compare gene enrichment values (GEV) among various immunologic cell types and immune markers with known associations with oncologic outcomes. RESULTS: We identified 424 patients with LAG3 expression and survival data in the TCGA BLCA cohort. Patients with low LAG3 expression had a statistically significant higher OS compared to patients with MIBC and lower expression (p=0.0006). When stratified by gender and age, receipt of chemotherapy, high LAG3 expression remainder significant prognostic factors for OS (p=0.023) (Figure 8B). As LAG-3 expression across immune cells, we compared LAG-3 expression across immune cell subtypes. High LAG-3 expression in muscle invasive bladder cancer (MIBC) decreased infiltration of CD8+/M2b macrophages/Th17/Tregs and B cells (p<0.001). Likewise, comparison of high and low LAG-3 expression demonstrated increased Treg expression, increased CD8+ T cell with enhanced PD1 expression, reflecting marked immunoevasive environment with CD8+ T cell dysfunction. CONCLUSIONS: Our study reported LAG-3+ cells abundance was an independent predictor for poor OS in MIBC patients within TCGA cohort. Blockade with LAG-3 inhibitors in bladder cancer is critical to explore as potential novel adjunctive therapy. Source of Funding: NA © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e302 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Tamir Sholklapper More articles by this author Laura Bukavina More articles by this author Andres Correa More articles by this author Alexander Kutikov More articles by this author Philip Abbosh More articles by this author Expand All Advertisement PDF downloadLoading ...