The Prognostic Significance of Programmed Death-Ligand 1 (PD-L1) in Skin Neoplasms: A Systematic Review and Meta-Analysis

Background and Aims Programmed death-ligand 1 (PD-L1) is an immune checkpoint molecule with proven therapeutic and prognostic implications. However, its prognostic significance in skin neoplasms remains controversial. In this study, we aimed to evaluate the prognostic value of PD-L1 expression in skin neoplasms. Methods We systematically searched PubMed, Scopus, and Web of Science databases up to March 2025, to evaluate overall survival (OS) and disease-free survival (DFS) as outcome measures. Subgroup analyses were performed based on tumor type. Heterogeneity and publication bias were assessed using I² statistics and funnel plots, respectively. Results A total of 24 studies were included. In the meta-analysis of OS on 12 studies, PD-L1 expression was not significantly associated with survival [HR = 0.89, 95% CI: 0.70-1.12]. However, subgroup analysis showed that PD-L1 expression was associated with improved OS in Merkel cell carcinoma [HR = 0.39, 95% CI: 0.18-0.83]. For DFS (8 studies), PD-L1 expression showed no significant overall association [random-effects HR = 0.86, 95% CI: 0.54-1.38], but it predicted better DFS in melanoma and cutaneous squamous cell carcinoma, and worse DFS in cutaneous angiosarcoma and sebaceous gland carcinoma. Additionally, in squamous cell carcinoma, PD-L1 expression was significantly associated with the risk of lymph node metastasis [OR = 5.33, 95% CI: 2.21-12.89]. Conclusion The prognostic significance of PD-L1 expression in skin neoplasms appears to be subtype-specific, correlating with improved survival in some cancers such as Merkel cell carcinoma, but with worse outcomes in others like cutaneous angiosarcoma and sebaceous gland carcinoma.