PD47-05 REGULATORY T CELLS PLAY A KEY ROLE IN BLADDER CANCER DEVELOPMENT

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology IV (PD47)1 Apr 2020PD47-05 REGULATORY T CELLS PLAY A KEY ROLE IN BLADDER CANCER DEVELOPMENT Karen Wheeler*, Niannan Ji, Neelam Mukherjee, and Robert Svatek Karen Wheeler*Karen Wheeler* More articles by this author , Niannan JiNiannan Ji More articles by this author , Neelam MukherjeeNeelam Mukherjee More articles by this author , and Robert SvatekRobert Svatek More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000934.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Regulatory T cells (Treg) are vital in the development and maintenance of immune tolerance. They function to dampen immune responses and their dysfunction leads to autoimmune disease. Treg are known to play key roles in the development of cancers including lung, breast, head and neck, and others. They are believed to aid the tumors in immune evasion. In bladder cancer (BCa), clinical studies have shown an increase in Treg in patients’ tumors or peripheral blood correlates with a worse prognosis. Herein we determine whether Treg play a key role in the development of BCa. METHODS: Female wild type C57BL/6 mice or transgenic DEREG mice (express a diptheria toxin [DT] receptor whenever Foxp3, the driver of a Treg phenotype, is expressed) were used. Metastatic cancer was induced by injecting 0.5 x 106 MB49 bladder tumor cells via tail vein into mice on the day of surgery. Orthotopic (bladder) cancer was induced by catheterizing the bladders of female mice and injecting poly-L-lysine followed by 0.08x106 MB49 cells at day 0. Treg were depleted in DEREG mice with administration of 50g/kg DT given intraperitoneally every 4 days. Mice were sacrificed at days 21-26 and bladders, lungs, and bladder draining lymph nodes (BLN) were harvested for weight and flow cytometric analysis. RESULTS: In mice that received both orthotopic and intravenous bladder tumor challenge, Treg were increased in the bladder tumors but not the lymph nodes or lung (Fig 1). In DEREG mice challenged with orthotopic BCa, depletion of Treg with DT administration abrogated the development of BCa (Fig 2A). Additionally, Treg depleted mice had an increase in the number and percentage of antigen specific CD8+ T cells in the bladder draining lymph nodes as well as an increase in activated CD4+ T cells (Fig 2B). CONCLUSIONS: Regulatory T cells are necessary for BCa development in the orthotopic model of BCa. Treg appear to function in an antigen-specific manner, but pan-T cell activation cannot be excluded. Development of immunotherapy targeting Treg in the bladder may represent a novel cancer therapeutic. Source of Funding: AUA Care Foundation Award, CPRIT Training Grant © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e927-e927 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Karen Wheeler* More articles by this author Niannan Ji More articles by this author Neelam Mukherjee More articles by this author Robert Svatek More articles by this author Expand All Advertisement PDF downloadLoading ...