Mp65-04 Co-Inhibitory Receptors in Non-Urothelial Bladder Cancer–targets for Next Generation Immunotherapy

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology III (MP65)1 May 2024MP65-04 CO-INHIBITORY RECEPTORS IN NON-UROTHELIAL BLADDER CANCER–TARGETS FOR NEXT GENERATION IMMUNOTHERAPY Lennert Eismann, Stephan Ledderose, Julian Marcon, Robert Bischoff, Raphaela Waidelich, Gerald Schulz, Jozefina Casuscelli, Christian Stief, and Severin Rodler Lennert EismannLennert Eismann , Stephan LedderoseStephan Ledderose , Julian MarconJulian Marcon , Robert BischoffRobert Bischoff , Raphaela WaidelichRaphaela Waidelich , Gerald SchulzGerald Schulz , Jozefina CasuscelliJozefina Casuscelli , Christian StiefChristian Stief , and Severin RodlerSeverin Rodler View All Author Informationhttps://doi.org/10.1097/01.JU.0001008756.24343.22.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The response to platin-based chemotherapy in non-urothelial variants of bladder cancer is poor. Current trials focus on PD-L1/PD-1 receptor inhibition but co-inhibitory receptors might play a crucial role and present alternative targets for immunotherapy. The expression of T-cell immunoglobulin and mucin domain-containing-3 (TIM-3), lymphocyte activation gene 3 (LAG-3), and T-cell immunoreceptor with Ig and ITIM domains (TIGIT) has not been investigated in non-urothelial bladder cancer. METHODS: We included patients with squamous cell carcinoma (SSC) and adenocarcinoma (ADENO) from a large prospectively maintained database of patients undergoing radical cystectomy for bladder cancer at our academic center. First, tissue microarrays were created from different tumor areas of representative FFPE samples. Immunohistochemical staining for TIM-3, LAG-3 and TIGIT was performed. Kaplan-Meier-method and Cox regression models were used to calculate differences in overall survival (OS) and progression free survival (PFS). RESULTS: In total, 59 patients with SCC and 24 patients with ADENO were included. TIM-3 was expressed in 24/59 (40.7%) of SCC and in 8/24 (33.3%) of all ADENO patients (p=0.632), LAG-3 in 27/59 (45.8%) of SCC and in 0/24 (0.0%) of all Adeno patients (p<0.001) and TIGIT in 27/59 patients (45.8%) of all SCC and in 12/24 (50.0%) of all ADENO patients (p=0.810). All three inhibitory co-receptors were expressed in 15 (25.4%) SCC but no (0/24) in ADENO. 20 (33.9%) SCC and 10 (41.6%) ADENO revealed no expression of the respective co-receptors. TIM-3 expression is associated with poor PFS (TIM-3high: 6 months vs. TIM-3low: not reached, p=0.048) in SCC whereas LAG-3 or TIGIT are not. OS was not different for SCC or ADENO based on inhibitory co-receptor expression. CONCLUSIONS: Coinhibitory receptors are differently expressed in squamous cell carcinoma and adenocarcinoma of the bladder. Triple-positive patients might be suitable for future immunotherapies but require biomarker testing in clinical trials. All three biomarkers are not prognostic for OS, but TIM-3 reveals prognostic potential for PFS in patients with SCC subtype. Source of Funding: No funding © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e1078 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Lennert Eismann More articles by this author Stephan Ledderose More articles by this author Julian Marcon More articles by this author Robert Bischoff More articles by this author Raphaela Waidelich More articles by this author Gerald Schulz More articles by this author Jozefina Casuscelli More articles by this author Christian Stief More articles by this author Severin Rodler More articles by this author Expand All Advertisement PDF downloadLoading ...