MP06-11 CHARACTERIZATION OF INFLAMMATORY CELLS IN HUMAN BENIGN PROSTATIC HYPERPLASIA

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research & Pathophysiology (MP06)1 Apr 2020MP06-11 CHARACTERIZATION OF INFLAMMATORY CELLS IN HUMAN BENIGN PROSTATIC HYPERPLASIA Renee Vickman, Gregory Cresswell, Nadia Lanman, Meaghan Broman, Omar Franco, Brian Helfand, Alexander Glaser, Lori Katz, Jacqueline Petkewicz, Pooja Talaty, Susan Crawford, Timothy Ratliff, and Simon Hayward* Renee VickmanRenee Vickman More articles by this author , Gregory CresswellGregory Cresswell More articles by this author , Nadia LanmanNadia Lanman More articles by this author , Meaghan BromanMeaghan Broman More articles by this author , Omar FrancoOmar Franco More articles by this author , Brian HelfandBrian Helfand More articles by this author , Alexander GlaserAlexander Glaser More articles by this author , Lori KatzLori Katz More articles by this author , Jacqueline PetkewiczJacqueline Petkewicz More articles by this author , Pooja TalatyPooja Talaty More articles by this author , Susan CrawfordSusan Crawford More articles by this author , Timothy RatliffTimothy Ratliff More articles by this author , and Simon Hayward*Simon Hayward* More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000820.011AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Benign prostatic hyperplasia (BPH) is characterized by enlargement of the prostate and often associated with lower urinary tract symptoms. Inflammatory cells are abundant in BPH tissues, and high-grade inflammation has been demonstrated to limit the success of current therapies. However, the mechanisms by which immune cells influence BPH progression and therapy resistance are not well understood. The purpose of these studies is to characterize the subpopulations of inflammatory cells within small (<60 grams) versus large (>70 grams) human prostate tissues, representing the progression of BPH. METHODS: To define immune cell types throughout BPH progression, the transition zone was isolated from fresh human prostate tissues after robotic-assisted laparoscopic prostatectomy or simple prostatectomy. Samples were minced and digested, followed by cell sorting of viable, CD45+EpCAM-CD200- immune cells. The 10x Chromium System was used to perform single-cell mRNA-sequencing (scRNA-seq) on the isolated CD45+ cells from small or large prostate tissues. CellRanger and Seurat were used for data analysis, evaluation of cell clusters, and differential pathway analysis. RESULTS: CD45+ cells from ten small and four large tissues were evaluated from men ages 61-76. Patients with large prostates had a significantly increased International Prostate Symptom Score, but no significant differences in age or body mass index. CD45+ cells are more abundant in large versus small prostate tissues. Preliminary analysis using unsupervised clustering identified 14 immune cell clusters among all samples, with no significant changes in CD45+ subpopulations when comparing small and large samples. There may be a slight increase in B cell and plasma cell populations in patients with large prostates. Addition of cell surface protein markers aided in the classification of CD45+ cell types at the single-cell level and pathway analysis suggests altered cytokine signaling in samples from large versus small prostates. CONCLUSIONS: CD45+ immune cells are an abundant cell type in human BPH and accumulate in large prostate tissues. scRNA-seq of CD45+ cells identified an array of immune cell subtypes present, with similar proportions of immune cell types within BPH samples as the disease progresses. Ongoing studies will investigate alterations in cytokine signaling between CD45+ cells in these two groups. These studies will functionally characterize inflammation during BPH progression and identify signaling pathways that may be utilized for therapeutic targeting. Source of Funding: This work is funded by 1P20DK116185 and supported by the Rob Brooks Fund for Precision Prostate Cancer Care and Walther Cancer Foundation. © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e55-e55 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Renee Vickman More articles by this author Gregory Cresswell More articles by this author Nadia Lanman More articles by this author Meaghan Broman More articles by this author Omar Franco More articles by this author Brian Helfand More articles by this author Alexander Glaser More articles by this author Lori Katz More articles by this author Jacqueline Petkewicz More articles by this author Pooja Talaty More articles by this author Susan Crawford More articles by this author Timothy Ratliff More articles by this author Simon Hayward* More articles by this author Expand All Advertisement PDF downloadLoading ...