Efficacy of new immunotherapy agents in bladder cancer

The ex-vivo efficacy of immunotherapeutic agents as an oncogram in primary bladder cancer cell cultures obtained from patients with intermediate-risk and high-risk non-muscle invasive bladder cancer (NMIBC) and its possible relationships with clinicopathologic features were evaluated. In the study, fresh tumor tissues and peripheral blood samples were obtained from each patient at transurethral resection of the bladder tumor (TUR-BT) operated between 2018-2019. Mononuclear cells (MNCs) were isolated from blood samples. Primary bladder cancer cell cultures were produced from each tissue sample. Each culture was divided into 5 drug administration groups. In Group-1, MNCs and non-treated primary cells only were used. Besides MNCs, Mitomycin-C (MMC) for Group-2, Bacillus Calmette Guérin (BCG) for Group-3, Nivolumab for Group-4 and Ipilimumab for Group-5 were applied to cells. Viability tests were performed with using WST-1. Expressions of Programmed Death-1, its Ligand-1, Ligand-2 (PD-1, PD-L1 and PD-L2, respectively) and Cytotoxic T-lymphocyte Associated Antigen-4 (CTLA-4) were also investigated immunohistochemically (IHC). Viability rates of the applications, IHC results and clinicopathologic features in the groups were evaluated and compared to each other. Twenty cases were evaluated in this study. Tumoral PD-1 positivity was found to be significantly associated with worse pathological outcomes. All agents caused lower viability rates than own controls after the drug administrations. Good response rates of PD-L1 positive cases were found to be significantly higher compared to PD-L1 negative cases after the MMC (66% vs 0%, p=0.045) and Nivolumab (66% vs 0%, p=0.045) treatments. Also, good response rate after MMC was only found to be higher in high-risk cases with peritumoral PD-1 positive than negatives (87.5% vs 20%, p=0.032). In addition, 5 of 6 untreated patients who had a recurrence in follow-up showed good response rate for MMC in cell cultures (p=0.035). Drug responses, namely oncogram results obtained from the ex-vivo applications of MMC, BCG, Nivolumab and Ipilimumab were found to be significantly higher than controls. Although, there were some differences based on IHC and clinicopathologic features between the patients with intermediate-risk and high-risk NMIBC, Nivolumab response rate was found to be better especially in PD-L1 positive patients.