MP66-19 SURVEY OF B AND PLASMA CELLS IN BLADDER CANCER

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology III (MP66)1 Sep 2021MP66-19 SURVEY OF B AND PLASMA CELLS IN BLADDER CANCER Yuanshuo Wang, Jorge Daza, Giuliana Magri, Emilie Grasset, Kristin Beaumont, Adam Farkas, Li Wang, Rachel Brody, Reza Mehrazin, Peter Wiklund, Robert Sebra, Jun Zhu, Matthew Galsky, Nina Bhardwaj, John Sfakianos, and Amir Horowitz Yuanshuo WangYuanshuo Wang More articles by this author , Jorge DazaJorge Daza More articles by this author , Giuliana MagriGiuliana Magri More articles by this author , Emilie GrassetEmilie Grasset More articles by this author , Kristin BeaumontKristin Beaumont More articles by this author , Adam FarkasAdam Farkas More articles by this author , Li WangLi Wang More articles by this author , Rachel BrodyRachel Brody More articles by this author , Reza MehrazinReza Mehrazin More articles by this author , Peter WiklundPeter Wiklund More articles by this author , Robert SebraRobert Sebra More articles by this author , Jun ZhuJun Zhu More articles by this author , Matthew GalskyMatthew Galsky More articles by this author , Nina BhardwajNina Bhardwaj More articles by this author , John SfakianosJohn Sfakianos More articles by this author , and Amir HorowitzAmir Horowitz More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002106.19AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Tumor infiltrating B cells in bladder cancer (BCa) have been associated with cancer invasion, but little is understood regarding their role in the tumor microenvironment. In this study, we analyzed single cell sequencing data from tumor (n=19) and PBMC (n=20) samples from 26 BCa patients to profile the heterogeneity of B cells and plasma cells (PCs). METHODS: Single cell data was imported into R (v4.03) using the SingleCellExperiment package, and outliers in mitochondrial gene percentage, library size, or detected genes were discarded. Normalization, deconvolution, and library size adjustment were done using the scran and batchelor R packages. Trajectory analysis was done using the Monocle R package. RESULTS: We identified 3,158 CD45+ naïve, non-switched memory (NSM), and switched memory (SM) B cells and PCs according to their marker gene expression (Fig 1). The majority of naïve and memory B cells were from PBMC, whereas plasma cells were primarily from tumor. To understand the heterogeneity of PCs, we performed clustering and trajectory analysis on 1,411 PCs and identified eight clusters (Fig 2A). Though most clusters consisted mainly of tumor cells, clusters 7 is almost exclusively from PBMC and is at the beginning of the pseudotime trajectory (Fig 2A). Its lower expression of PC markers such as MZB1, XBP1, and immunoglobulin genes suggest that it’s at an earlier stage of PC maturation (Fig 2A). Clusters 1, 6, and 8 contain PCs likely representative of mature plasmablasts, as they are at the end of the pseudotime trajectory and express high levels PC markers and immunoglobulin genes (Fig 2A). Lastly, cluster 4 upregulates expression of HLA-DP, HLA-DQ, and HLA-DR genes further on the pseudotime trajectory (Fig 2B). CONCLUSIONS: From our survey of B cells and PCs from a large single cell BCa cohort, we observed the majority of PCs to be found in the tumor. Tumor PCs demonstrate a high degree of heterogeneity, encompassing at least an early stage subset, a more mature plasmablast-like subset, and another subset with upregulated HLA expression with potential for T-cell stimulatory function. Source of Funding: institutional funds © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1137-e1137 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yuanshuo Wang More articles by this author Jorge Daza More articles by this author Giuliana Magri More articles by this author Emilie Grasset More articles by this author Kristin Beaumont More articles by this author Adam Farkas More articles by this author Li Wang More articles by this author Rachel Brody More articles by this author Reza Mehrazin More articles by this author Peter Wiklund More articles by this author Robert Sebra More articles by this author Jun Zhu More articles by this author Matthew Galsky More articles by this author Nina Bhardwaj More articles by this author John Sfakianos More articles by this author Amir Horowitz More articles by this author Expand All Advertisement Loading ...