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.