The prognostic value of PD-L1 expression in upper tract urothelial carcinoma varies according to platelet count

Programmed cell death ligand-1 (PD-L1) is a ligand for programmed cell death-1 (PD-1) that negatively regulates T-cell activation and plays a crucial role in suppressing anti-tumor host immunity. Although PD-L1 is a promising immunotherapy target in various cancers, including urothelial carcinoma (UC), the prognostic significance of PD-L1 in UC is unclear. As platelets help protect tumor cells from immune elimination in the circulatory system, we hypothesized that tumor PD-L1 and circulating platelets might synergistically promote tumor metastasis, and that the prognostic significance of PD-L1 might vary according to platelet count. We immunohistochemically examined tumor PD-L1 expression in 271 patients with upper tract UC, which revealed PD-L1 positivity in 31 of 271 cases (11%). The associations of tumor PD-L1 expression with outcomes varied among patients with high or low platelet counts (P_interaction  < 0.004). Among patients with high platelet counts (N = 136), PD-L1 positivity (N = 15) was significantly associated with shorter metastasis-free survival (univariate hazard ratio [HR]: 6.23, 95% confidence interval [CI]: 2.95-13.1; multivariate HR: 2.68, 95% CI: 1.27-5.64) and shorter overall survival (univariate HR: 4.92, 95% CI: 2.14-11.3, multivariate HR: 2.78, 95% CI: 1.19-6.51). In contrast, among patients with low platelet counts (N = 135), PD-L1 positivity (N = 16) was not significantly associated with these outcomes. Our results suggest that tumor PD-L1 expression and platelet count might interact and help regulate tumor progression. Although a larger prospective study is needed to validate our findings, this relationship is important to consider, as immunotherapies targeting the PD-1/PD-L1 axis have gained significant attention as promising therapies for UC.