MP04-14 T CELL AND B CELL RECEPTOR SEQUENCING REVEALS ANTI-CANCER IMMUNE RESPONSE ASSOCIATED WITH IMMUNE-RELATED ADVERSE EVENTS IN ADVANCED RENAL CELL CARCINOMA PATIENTS TREATED WITH IMMUNE CHECKPOINT INHIBITORS

Abstract

You have accessJournal of UrologyCME1 Apr 2023MP04-14 T CELL AND B CELL RECEPTOR SEQUENCING REVEALS ANTI-CANCER IMMUNE RESPONSE ASSOCIATED WITH IMMUNE-RELATED ADVERSE EVENTS IN ADVANCED RENAL CELL CARCINOMA PATIENTS TREATED WITH IMMUNE CHECKPOINT INHIBITORS Taigo Kato, Kazuma Kiyotani, Yu Ishizuya, Yoshiyuki Yamamoto, Koji Hatano, Atsunari Kawashima, and Norio Nonomura Taigo KatoTaigo Kato More articles by this author , Kazuma KiyotaniKazuma Kiyotani More articles by this author , Yu IshizuyaYu Ishizuya More articles by this author , Yoshiyuki YamamotoYoshiyuki Yamamoto More articles by this author , Koji HatanoKoji Hatano More articles by this author , Atsunari KawashimaAtsunari Kawashima More articles by this author , and Norio NonomuraNorio Nonomura More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003215.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Recently, several data are available on the relationship between immune-related adverse events (irAEs) and clinical efficacy in patients with immune checkpoint inhibitors (ICIs). In this study, we aimed to elucidate T cell receptor (TCR) and B cell receptor (BCR) repertoire in peripheral blood mononuclear cells (PBMCs) before and after ICI treatment, and at the onset of irAE for understanding of irAE-induced anti-cancer immune responses. METHODS: We collected metastatic tumor tissues and peripheral blood samples from 56 patients with advanced renal cell carcinoma before and 1 month after anti-programmed cell death protein 1 (PD-1) treatment initiation. Furthermore, we applied a next-generation sequencing approach to characterize TCR and BCR repertoires using tumor tissues and PBMCs. RESULTS: The number of irAEs was significantly higher in responder for PD-1 treatment (p<0.0001). TCR repertoire analysis revealed that diversity index (DI) for TCR alpha and beta in irAE present patients were significantly decreased at 1 month after treatment, indicating expansion of certain T cell clones even in PBMCs after the treatment (Figure 1A). We also examined morisita index to measure T cell similarity between pre- and post- treatment than irAE absent patients, indicating a larger change in the T cell clones, and inducing newly expanded T cells in post- treatment PBMC samples (Figure 1B). Importantly, irAE present patients had significantly higher numbers of peripheral T cell clones shared with metastatic tumor-infiltrating T cells than those in irAE absent patients at 1 month after treatment (p=0.038). We also confirmed that DI for BCR IgM and IgG in irAE present patients were significantly decreased at 1 month after the treatment, indicating expansion of certain B cell clones (Figure 1C). CONCLUSIONS: Our findings revealed that a certain number of irAE-induced T cell and B cell clones can circulate systemically and attack tumor cells synergistically in distant regions, leading to durable response in the patients with irAEs. Source of Funding: This work was supported by JSPS KAKENHI (Grant-in-Aid for Scientific Research (C), grant number 18K09133 and 21K09343 © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e38 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Taigo Kato More articles by this author Kazuma Kiyotani More articles by this author Yu Ishizuya More articles by this author Yoshiyuki Yamamoto More articles by this author Koji Hatano More articles by this author Atsunari Kawashima More articles by this author Norio Nonomura More articles by this author Expand All Advertisement PDF downloadLoading ...