MP83-09 TUMOR NECROSIS FACTOR-RELATED APOPTOSIS-INDUCING LIGAND (TRAIL) POTENTIATES THE EFFECT OF BACILLUS CALMETTE-GUÉRIN (BCG) IN UROTHELIAL CARCINOMA MODEL

Abstract

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 (n1⁄45,1 vial Tice suspended in 50ml saline), cisplatin (n1⁄45, 1mg/ml), or saline (n1⁄45) 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%, p1⁄40.12) or CD8+ cells (19.3% vs 16.4%, p1⁄40.28) 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, p1⁄40.15), Foxp3+ CD4+ cells (13.9% vs 16.4%, p1⁄40.25), or CD8+ cells (16.4% vs 16.9%, p1⁄40.85) 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.