MP66-16 EX-VIVO ASSESSMENT OF T CELL RESPONSE TO CHECKPOINT INHIBITION IN BLADDER AND KIDNEY TUMORS

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology III (MP66)1 Sep 2021MP66-16 EX-VIVO ASSESSMENT OF T CELL RESPONSE TO CHECKPOINT INHIBITION IN BLADDER AND KIDNEY TUMORS Elizabeth Koehne, Hiten Patel, Lourdes Plaza Rojas, Michael Delos Reyes, Alex Belshoff, Nicholas Elliott, Alex Gorbonos, Michael Woods, Marcus Quek, Gopal Gupta, and Jose Guevara-Patino Elizabeth KoehneElizabeth Koehne More articles by this author , Hiten PatelHiten Patel More articles by this author , Lourdes Plaza RojasLourdes Plaza Rojas More articles by this author , Michael Delos ReyesMichael Delos Reyes More articles by this author , Alex BelshoffAlex Belshoff More articles by this author , Nicholas ElliottNicholas Elliott More articles by this author , Alex GorbonosAlex Gorbonos More articles by this author , Michael WoodsMichael Woods More articles by this author , Marcus QuekMarcus Quek More articles by this author , Gopal GuptaGopal Gupta More articles by this author , and Jose Guevara-PatinoJose Guevara-Patino More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002106.16AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Checkpoint inhibitors (CPI) have emerged as a way to activate the immune system’s antitumor properties by blocking inhibitory signals such as programmed cell death ligand 1 and programmed cell death protein 1. Systemic CPI can treat Bacillus Calmette–Guérin-unresponsive and advanced bladder cancer, and are also used in advanced kidney cancer. However, only 20-30% of patients experience a clinical response to CPI and there is no test available to determine which patients may respond to each agent. We aimed to see if tumor specimens incubated with a panel of CPI would demonstrate different T cell responses ex vivo. METHODS: Patients undergoing surgical resection of bladder and kidney tumors were prospectively enrolled in the study. Eleven bladder cancer (4 low-grade and 7 high-grade) and 4 kidney cancer specimens were included. Approximately 1 cm3 of fresh tumor was obtained and divided into 4 fragments. One piece was left untreated and the remaining 3 were incubated separately with atezolizumab, nivolumab, and pembrolizumab for 24 hours. A cell suspension was created with each specimen. Fluorochrome-conjugated antibodies against Fc-receptor, CD3, CD4, and CD8 were used to stain the cells and analysis was performed by flow cytometry. Dead cells were excluded from analysis by using Zombie Aqua viability dye (BioLegend). Tumor-infiltrating T-cells were gated as CD3+ cells. Response to treatment was defined as a greater than 1-fold change in % live T cells compared to the untreated specimen. RESULTS: Thirteen of 15 specimens (86.7%) demonstrated an increase in T cells with at least one of the treatments. Five of 15 specimens (33.3%) had an increase with all 3 treatments. Amongst samples with a positive response to atezolizumab (n=9), median increase in % live T cells was 2.48-fold (interquartile range (IQR) 1.33-4.61) (Figure 1). The median increase in % live T cells in nivolumab responders (n=8) was 2.31-fold (IQR 1.93-2.41), and median increase in pembrolizumab responders (n=11) was 1.68 (IQR 1.47-2.23). CONCLUSIONS: Different tumor microenvironment T-cell responses to CPI can be characterized using flow cytometry of fresh tissue from patients undergoing surgery for management of bladder and kidney cancer. This assay may be used in the future to better predict which patients will respond to immunotherapy. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1135-e1135 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Elizabeth Koehne More articles by this author Hiten Patel More articles by this author Lourdes Plaza Rojas More articles by this author Michael Delos Reyes More articles by this author Alex Belshoff More articles by this author Nicholas Elliott More articles by this author Alex Gorbonos More articles by this author Michael Woods More articles by this author Marcus Quek More articles by this author Gopal Gupta More articles by this author Jose Guevara-Patino More articles by this author Expand All Advertisement Loading ...