PD-L1 Assessment in Merkel Cell Carcinoma: Predictive Implications for Anti-PD-1 and Anti-PD-L1 Therapy

Background: Merkel cell carcinoma (MCC) is an aggressive skin cancer with high risk of metastasis and poor prognosis.Immune checkpoint inhibitors (ICI) targeting programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1) have improved clinical outcomes, but reliable predictive biomarkers for therapy response remain lacking.This study investigates tumor PD-L1 expression as a potential predictive marker for ICI therapy response in MCC patients. Methods: Pre-treatment tumor samples from MCC patients were collected and assessed for PD-L1 expression via immunohistochemistry (cut-off: 1%).Clinical outcomes including best overall response (BOR), progression-free survival (PFS), and overall survival (OS), were compared based on tumor PD-L1 status and ICI therapy type in this single-center study.Results: Patients treated with anti-PD-1 (n=18) or anti-PD-L1 (n=21) therapy were included, of whom 23/39 patients (59%) had PD-L1 positive MCC.Patients with PD-L1 positive MCC showed significantly improved OS (HR=0.358;95%CI=0.144-0.882;p=0.018) and a trend toward longer PFS (HR=0.594;95%CI=0.287-1.230;p=0.125).Among patients with PD-L1 positive MCC, those treated with anti-PD-1-based ICI achieved CR/PR more frequently (OR=0.190;95%CI=0.032-1.145;p=0.074) and demonstrated significantly prolonged PFS (HR= 3.001; 95%CI=1.060-8.494;p=0.019) compared with patients receiving anti-PD-L1based therapy.Conclusion: Patients with PD-L1 positive MCC tended to show a better BOR, a prolonged PFS and a significantly longer OS under ICI treatment compared to patients with PD-L1 negative MCC.Furthermore, patients with PD-L1 positive MCC benefited especially from anti-PD-1-based ICI.These findings support the role of PD-L1 as a predictive biomarker in MCC and highlight potential differences in efficacy between anti-PD-1-and anti-PD-L1-based ICI.