PD-L1 assessment in Merkel cell carcinoma: Predictive implications for anti-PD-1 and anti-PD-L1 therapy

Schielke, Lisa; Thielmann, Carl Maximilian; Schadendorf, Dirk; Abrecht, Lea Jessica; Kretz, Julia; Lodde, Georg; Ugurel, Selma; Dissemond, Joachim; Roesch, Alexander; Sucker, Antje; Dalkoohi, Mazdak; Hadaschik, Eva; Livingstone, Elisabeth; Becker, Jürgen; Placke, Jan-Malte; Zimmer, Lisa; Krefting, Frederik; Tasdogan, Alpaslan

doi:10.1016/j.ejcskn.2026.101126

Journal Article

DKFZ-2026-00857

PD-L1 assessment in Merkel cell carcinoma: Predictive implications for anti-PD-1 and anti-PD-L1 therapy

Schielke, L.DKFZ* ; Dalkoohi, M.DKFZ* ; Thielmann, C. M.DKFZ* ; Hadaschik, E.DKFZ* ; Dissemond, J.DKFZ* ; Abrecht, L. J.DKFZ* ; Kretz, J.DKFZ* ; Sucker, A.DKFZ* ; Lodde, G.DKFZ* ; Krefting, F.DKFZ* ; Roesch, A.DKFZ* ; Zimmer, L.DKFZ* ; Livingstone, E.DKFZ* ; Tasdogan, A.DKFZ* ; Becker, J.DKFZ* ; Schadendorf, D.DKFZ* ; Ugurel, S.DKFZ* ; Placke, J.-M.DKFZ*

2026
Elsevier B.V. Amsterdam

EJC skin cancer 4, 101126 (2026) [10.1016/j.ejcskn.2026.101126]

Abstract: Background: Merkel cell carcinoma (MCC) is an aggressive skin cancer with high risk of metastasis and poorprognosis. Immune checkpoint inhibitors (ICI) targeting programmed death-1 (PD-1) or programmed deathligand 1 (PD-L1) have improved clinical outcomes, but reliable predictive biomarkers for therapy responseremain lacking. This study investigates tumor PD-L1 expression as a potential predictive marker for ICI therapyresponse in MCC patients.Methods: Pre-treatment tumor samples from MCC patients were collected and assessed for PD-L1 expression viaimmunohistochemistry (cut-off: ≥ 1%). Clinical outcomes including best overall response (BOR), progressionfree survival (PFS), and overall survival (OS), were compared based on tumor PD-L1 status and ICI therapytype 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 23/39patients (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/PRmore 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-L1-based therapy.Conclusion: Patients with PD-L1 positive MCC tended to show a better BOR, a prolonged PFS and a significantlylonger OS under ICI treatment compared to patients with PD-L1 negative MCC. Furthermore, patients with PD-L1positive 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.

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