PD42-09 SINGLE CELL TRANSCRIPTOMICS OF MURINE BLADDER CANCER IMPLICATES ANDROGEN SIGNALING AND T CELL EXHAUSTION

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology II (PD42)1 Sep 2021PD42-09 SINGLE CELL TRANSCRIPTOMICS OF MURINE BLADDER CANCER IMPLICATES ANDROGEN SIGNALING AND T CELL EXHAUSTION Jessica Brown, Bradley Blaser, Jami Shaffer, Hyunwoo Kwon, Anil Parwani, William Carson, Zihai Li, Purnima Dubey, and Debasish Sundi Jessica BrownJessica Brown More articles by this author , Bradley BlaserBradley Blaser More articles by this author , Jami ShafferJami Shaffer More articles by this author , Hyunwoo KwonHyunwoo Kwon More articles by this author , Anil ParwaniAnil Parwani More articles by this author , William CarsonWilliam Carson More articles by this author , Zihai LiZihai Li More articles by this author , Purnima DubeyPurnima Dubey More articles by this author , and Debasish SundiDebasish Sundi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002056.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Recently single-cell RNA sequencing (scRNA-Seq) has increased our depth of understanding of genomic features of distinct cellular populations. To reveal the dynamics of bladder carcinogenesis, we applied a scRNA-Seq based analysis to murine bladders undergoing malignant transformation secondary to exposure to N-Butyl-N-(4-hydroxybutyl) nitrosamine (BBN). METHODS: 4 week old female C57BL6 mice (Jackson Labs) were exposed to 0.05% BBN ad libitum in drinking water for up to 20 weeks. At 5, 10, 17 weeks, and 23 weeks after the start of BBN exposure, bladders harvested and processed into a single cell suspension for scRNA-Seq (10x Genomics). RESULTS: Under these conditions, histologic evidence of urothelial dysplasia was detected at 5-10 weeks, and high grade carcinoma in situ (CIS) by 17-23 weeks. Several bladder cancer intrinsic subtype signatures were presents, suggesting broad generalizability to human cancer. Over time, urothelial and myeloid immune cell clusters demonstrated enrichment of several druggable target such as EGFR, FGFR3, and HIF1A. The most significant change over time was an increase in androgen receptor (AR) expression within T cells. SLAMF6 and NR4A1 expression increased in parallel with AR in the T cell cluster, which is notable as all of these signals have likely roles in T cell exhaustion, which may permit carcinogenesis. CONCLUSIONS: During bladder carcinogenesis, androgen signaling pathways increase significantly within T cells. The T cell cluster also features parallel increases in gene expression related to exhaustion. These findings support the emerging link between androgen signaling and T cell exhaustion in bladder cancer pathogenesis. Source of Funding: Urology Care Foundation © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e727-e728 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jessica Brown More articles by this author Bradley Blaser More articles by this author Jami Shaffer More articles by this author Hyunwoo Kwon More articles by this author Anil Parwani More articles by this author William Carson More articles by this author Zihai Li More articles by this author Purnima Dubey More articles by this author Debasish Sundi More articles by this author Expand All Advertisement Loading ...