- Celal Bayar Üniversitesi Fen Bilimleri Dergisi
- Cilt: 21 Sayı: 3
- Modulation of PD-L1 Expression by Cisplatin and Gemcitabine in Bladder Cancer Cells
Modulation of PD-L1 Expression by Cisplatin and Gemcitabine in Bladder Cancer Cells
Authors : İhsan Nalkıran, Hatice Sevim Nalkıran
Pages : 28-34
Doi:10.18466/cbayarfbe.1593948
View : 52 | Download : 67
Publication Date : 2025-09-26
Article Type : Research Paper
Abstract :Bladder cancer (BC) incidence is rising globally, despite available treatment options, including tumor resection, systemic chemotherapy, and immune checkpoint inhibitors targeting PD-1/PD-L1. Gemcitabine and cisplatin are commonly combined as first-line systemic therapy, yet their effects on PD-L1 expression remain unclear. This study evaluated the effects of cisplatin and gemcitabine, alone and combined, on PD-L1 expression in a BC cell line, RT-4, and a normal epithelial cell line, ARPE-19. Cells were treated with IC20 doses of each drug, and PD-L1 expression was quantified by qRT-PCR after 48 hours. In ARPE-19 cells, cisplatin treatment induced a dose-dependent PD-L1 increase, peaking at a 59.6-fold elevation at higher doses (p < 0.001), while gemcitabine alone showed no effect. The combination of low-dose cisplatin and gemcitabine further elevated PD-L1 expression (25.2-fold, p < 0.05). In contrast, in RT-4 cells, low-dose cisplatin downregulated PD-L1, but higher doses resulted in a 61.3-fold increase (p < 0.05). Gemcitabine alone downregulated PD-L1 in RT-4 cells; however, the combined treatment produced a 99.4-fold upregulation (p < 0.001). These findings highlight dose- and cell type-specific effects of cisplatin and gemcitabine on PD-L1 regulation, with combination therapy notably upregulating PD-L1 in BC cells. This underscores the potential for integrating chemotherapy with immune checkpoint inhibitors to counteract chemotherapy-induced immune evasion in BC. Differential responses between normal and cancer cells emphasize the need for tumor-specific therapeutic approaches and further research on PD-L1 regulation to optimize immune checkpoint therapy.Keywords : Bladder cancer, PD-L1, cisplatin, gemcitabine, combination therapy
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