[Efficacy of combined treatment with pirfenidone and PD-L1 inhibitor in mice bearing ectopic bladder cancer xenograft].

OBJECTIVE

To assess the efficacy of pirfenidone combined with PD-L1 inhibitor for treatment of bladder cancer in a mouse model and its effect on tumor immune microenvironment modulation.

METHODS

Forty C57BL/6 mouse models bearing ectopic human bladder cancer xenografts were randomized into control group, PD-L1 inhibitor group, pirfenidone group and combined treatment group (=10). After successful modeling, PD-L1 inhibitor treatment was administered via intraperitoneal injection at 12.5 mg/kg every 3 days, and oral pirfenidone (500 mg/kg) was given on a daily basis. The survival rate of the mice and tumor growth rate were compared among the 4 groups. The expressions of CD3, CD8, CD45, E-cadherin and N-cadherin in the tumor tissues were detected with immunohistochemistry after the 21-day treatment, and bone marrow-derived suppressor cells (MDSCs) were observed with immunofluorescence staining; serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea nitrogen (BUN), creatinine (CRE) and lactate dehydrogenase (LDH-L) were analyzed using an automated biochemical analyzer.

RESULTS

Treatment with PD-L1 inhibitor and pirfenidone alone both significantly decreased tumor growth rate and tumor volume at 21 days ( < 0.05), but the combined treatment produced an obviously stronger inhibitory effect ( < 0.05). PD-L1 inhibitor and pirfenidone alone significantly increased E- cadherin expression and decreased N-cadherin expression in the tumor tissue ( < 0.05). The two treatments both significantly increased the percentage of CD3, CD8 and CD45 T cells and decreased the percentage of Ly-6GCD11bMDSCs in the tumor tissue, and these changes were more obvious in the combined treatment group ( < 0.05). No significant differences were found in serum ALT, AST, BUN, CRE or LDH-L levels among the 4 groups (>0.05).

CONCLUSION

Combined treatment with pirfenidone and PD-L1 inhibitor significantly inhibits the progression of bladder cancer in mice possibly by regulating tumor immune microenvironment and inhibiting epithelial-mesenchymal transition of the tumor cells.