MP83-08 LOCAL T LYMPHOCYTE SUB-POPULATION RESPONSES TO INTRAVESICAL BCG AND CHEMOTHERAPY IN AN IMMUNE COMPETENT MURINE MODEL OF BLADDER CANCER

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology IV1 Apr 2016MP83-08 LOCAL T LYMPHOCYTE SUB-POPULATION RESPONSES TO INTRAVESICAL BCG AND CHEMOTHERAPY IN AN IMMUNE COMPETENT MURINE MODEL OF BLADDER CANCER Max Kates, Nikolai Sopko, Hotaka Matsui, Xiaopu Liu, Leonardo Reis, Noah Hahn, Alex Baras, Christina Kochel, Charles Drake, and Trinity Bivalacqua Max KatesMax Kates More articles by this author , Nikolai SopkoNikolai Sopko More articles by this author , Hotaka MatsuiHotaka Matsui More articles by this author , Xiaopu LiuXiaopu Liu More articles by this author , Leonardo ReisLeonardo Reis More articles by this author , Noah HahnNoah Hahn More articles by this author , Alex BarasAlex Baras More articles by this author , Christina KochelChristina Kochel More articles by this author , Charles DrakeCharles Drake More articles by this author , and Trinity BivalacquaTrinity Bivalacqua More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2190AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES It has previously been shown that CD4 and CD8 cells are necessary to achieve BCG mediated antitumor reponses. Prior studies have also shown increases in the peripheral blood of pro-inflammatory CD4 cells and cytokines. However, it is currently unknown how infiltrating lymphocyte populations in bladder tumors change with intravesical therapy. The objective of the present study was to understand the effect of intravesical BCG and platinum-based chemotherapy on T cell subpopulations in an immune competent murine model of non-muscle invasive bladder cancer. METHODS Fischer 344 rats aged 7 weeks received 1.5mg/kg N-Nitroso-N-methylurea (MNU) every other week for 6 weeks (4 doses). Dysplasia begins by week 8 and by week 16 the majority of rats have a NMIBC phenotype with a mix of CIS, high grade Ta, and T1 disease. Beginning week 8 following the first MNU dose, rats were intravesically administered 0.3ml of BCG (n=5,1 vial Tice® suspended in 50ml saline), cisplatin (n=5, 1mg/ml), or saline (n=5) weekly for 6 total doses. All animals were sacrificed at week 16, and bladders (including tumors) were digested into single cell suspensions for flow cytometry. T lymphocyte subpopulations were then compared between the 3 groups using one-way ANOVA tests. RESULTS After whole bladder digestion, samples yielded 1-2 million cells per bladder. Rats treated with BCG had a 42% rise in CD4+ cells compared to saline controls (51.4% vs 34.8%, p<0.001). No significant differences in FoxP3+ CD4+ cells (20.6% vs 16.4%, p=0.12) or CD8+ cells (19.3% vs 16.4%, p=0.28) were observed between animals receiving BCG and saline control. Animals receiving intravesical cisplatin had no significant differences in CD4+ (34.8% in cisplatin vs 29.5% in controls, p=0.15), Foxp3+ CD4+ cells (13.9% vs 16.4%, p=0.25), or CD8+ cells (16.4% vs 16.9%, p=0.85) compared to animals receiving saline controls. CONCLUSIONS In an immune competent murine model of bladder cancer, our analysis of lymphocytes in the bladder wall suggests that BCG induces a large increase in CD4+ effector T cells, without a significant change in Foxp3+ regulatory T cells or CD8+ T cells. This large Th1 anticancer immunosurveillance response is not seen with intravesical platinum based chemotherapy. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e1083-e1084 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Max Kates More articles by this author Nikolai Sopko More articles by this author Hotaka Matsui More articles by this author Xiaopu Liu More articles by this author Leonardo Reis More articles by this author Noah Hahn More articles by this author Alex Baras More articles by this author Christina Kochel More articles by this author Charles Drake More articles by this author Trinity Bivalacqua More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...