PD-L1 in Merkel Cell Carcinoma: From Tumor Microenvironment to Pathological Interpretation.
5 affiliations
- 1PhD Program in Translational Molecular Medicine and Surgery, Department of Biomedical Sciences, Dental Sciences and Morpho-Functional Imaging, University of Messina, 98125 Messina, Italy.
- 2Department of Human Pathology of Adults and Developmental Age "Gaetano Barresi", Division of Pathology, University of Messina, 98125 Messina, Italy.
- 3Section of Molecular Pathology, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari "Aldo Moro", 70124 Bari, Italy.
- 4S.S.D. C.O.r.O. Bed Management Presa in Carico, TDM, IRCCS Istituto Tumori "Giovanni Paolo II", 70124 Bari, Italy.
- 5Medical Oncology Unit, Department of Human Pathology "G. Barresi", University of Messina, 98125 Messina, Italy.
Abstract
Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous neuroendocrine carcinoma in which Merkel cell polyomavirus (MCPyV) oncoproteins and ultraviolet-induced mutations provide distinct sources of tumor immunogenicity. This narrative review examines the biological determinants, immunohistochemical assessment, and prognostic and therapeutic relevance of programmed death ligand 1 (PD-L1) in MCC, linking tumor immunobiology to pathological interpretation. PD-L1 expression on tumor and immune cells is often concentrated at tumor-immune interfaces, consistent with interferon-γ-driven adaptive immune resistance. Reported associations with survival and treatment response vary across studies, partly reflecting differences in tissue sampling, assays, scoring compartments, and treatment context. Immune checkpoint blockade can produce durable responses in both PD-L1-positive and PD-L1-negative tumors, while baseline PD-L1 expression alone is not a validated criterion for treatment selection. Resistance mechanisms and emerging biomarkers are discussed alongside viral status, T-cell architecture, antigen-presentation defects, and alternative immune checkpoints. A reporting framework should emphasize specimen characteristics, assay documentation, separate assessment of PD-L1 expression in tumor and immune cells, and spatial heterogeneity. Interpreting PD-L1 within this biological and pathological context supports informative reporting and highlights the potential of integrated spatial biomarkers to improve understanding of immune responsiveness in MCC.
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BibTeX
@article{pepe2026pdl1,
title = {{PD-L1 in Merkel Cell Carcinoma: From Tumor Microenvironment to Pathological Interpretation.}},
author = {Ludovica Pepe and Vincenzo Fiorentino and Mario Della Mura and Alessandro Rizzo and Mariacarmela Santarpia and Antonio Ieni and Gerardo Cazzato and Maria Lentini},
journal = {International journal of molecular sciences},
year = {2026},
month = sep,
doi = {10.3390/ijms27198460},
url = {https://europepmc.org/article/MED/42883708},
note = {CC BY},
}
RIS
TY - JOUR
TI - PD-L1 in Merkel Cell Carcinoma: From Tumor Microenvironment to Pathological Interpretation.
AU - Ludovica Pepe
AU - Vincenzo Fiorentino
AU - Mario Della Mura
AU - Alessandro Rizzo
AU - Mariacarmela Santarpia
AU - Antonio Ieni
AU - Gerardo Cazzato
AU - Maria Lentini
PY - 2026
DA - 2026/09/23
JO - International journal of molecular sciences
DO - 10.3390/ijms27198460
UR - https://europepmc.org/article/MED/42883708
AB - Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous neuroendocrine carcinoma in which Merkel cell polyomavirus (MCPyV) oncoproteins and ultraviolet-induced mutations provide distinct sources of tumor immunogenicity. This narrative review examines the biological determinants, immunohistochemical assessment, and prognostic and therapeutic relevance of programmed death ligand 1 (PD-L1) in MCC, linking tumor immunobiology to pathological interpretation. PD-L1 expression on tumor and immune cells is often concentrated at tumor-immune interfaces, consistent with interferon-γ-driven adaptive immune resistance. Reported associations with survival and treatment response vary across studies, partly reflecting differences in tissue sampling, assays, scoring compartments, and treatment context. Immune checkpoint blockade can produce durable responses in both PD-L1-positive and PD-L1-negative tumors, while baseline PD-L1 expression alone is not a validated criterion for treatment selection. Resistance mechanisms and emerging biomarkers are discussed alongside viral status, T-cell architecture, antigen-presentation defects, and alternative immune checkpoints. A reporting framework should emphasize specimen characteristics, assay documentation, separate assessment of PD-L1 expression in tumor and immune cells, and spatial heterogeneity. Interpreting PD-L1 within this biological and pathological context supports informative reporting and highlights the potential of integrated spatial biomarkers to improve understanding of immune responsiveness in MCC.
SN - 1422-0067
ER -