PD-L1 promotes malignant progression by inducing EMT and enhancing stemness in muscle-invasive bladder cancer
Abstract Objective: Despite radical treatment for aggressive muscle-invasive bladder cancer(MIBC), the prognosis remained poor. Programmed cell death ligand 1(PD-L1) plays an important role in suppressing immune responses.We investigate if PD-L1 and EMT synergistically contribute to MIBC progression. Methods: In vitro experiments, we evaluated the effects of PD-L1 on proliferation, invasion, migration of MIBC cells and studied the relationship between PD-L1 and CSC/EMT markers by overexpressing and knocking down PD-L. The association of PD-L1 with EMT was detected in MIBC human specimens and the synergistic effect of PD-L1and EMT was assessed by analysis of overall survival (OS). Results: Our data demonstrated that PD-L1 promotes proliferation, invasion and migration of MIBC cells. The positive correlation between PD-L1 and CSC/EMT markers was verified both in vitro experiments and in 130 MIBC specimens. Moreover, patients with positive PD-L1/positive EMT exhibited poorer overall survival than patients with other combinations. Conclusion: The close relationship between PD-L1 and EMT may offer potential therapeutic strategy that co-targeting PD-L1 and EMT may improve the prognosis of MIBC patients.