{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T09:02:57Z","timestamp":1790154177890,"version":"4.0.1"},"reference-count":129,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>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\u2013immune interfaces, consistent with interferon-\u03b3-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.<\/jats:p>","DOI":"10.3390\/ijms27198460","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T08:14:39Z","timestamp":1790151279000},"page":"8460","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["PD-L1 in Merkel Cell Carcinoma: From Tumor Microenvironment to Pathological Interpretation"],"prefix":"10.3390","volume":"27","author":[{"given":"Ludovica","family":"Pepe","sequence":"first","affiliation":[{"name":"PhD Program in Translational Molecular Medicine and Surgery, Department of Biomedical Sciences, Dental Sciences and Morpho-Functional Imaging, University of Messina, 98125 Messina, Italy"},{"name":"Department of Human Pathology of Adults and Developmental Age \u201cGaetano Barresi\u201d, Division of Pathology, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1132-1761","authenticated-orcid":false,"given":"Vincenzo","family":"Fiorentino","sequence":"additional","affiliation":[{"name":"PhD Program in Translational Molecular Medicine and Surgery, Department of Biomedical Sciences, Dental Sciences and Morpho-Functional Imaging, University of Messina, 98125 Messina, Italy"},{"name":"Department of Human Pathology of Adults and Developmental Age \u201cGaetano Barresi\u201d, Division of Pathology, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5116-2484","authenticated-orcid":false,"given":"Mario","family":"Della Mura","sequence":"additional","affiliation":[{"name":"Section of Molecular Pathology, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5257-8678","authenticated-orcid":false,"given":"Alessandro","family":"Rizzo","sequence":"additional","affiliation":[{"name":"S.S.D. C.O.r.O. Bed Management Presa in Carico, TDM, IRCCS Istituto Tumori \u201cGiovanni Paolo II\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariacarmela","family":"Santarpia","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit, Department of Human Pathology \u201cG. Barresi\u201d, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2878-3572","authenticated-orcid":false,"given":"Antonio","family":"Ieni","sequence":"additional","affiliation":[{"name":"Department of Human Pathology of Adults and Developmental Age \u201cGaetano Barresi\u201d, Division of Pathology, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0325-4316","authenticated-orcid":false,"given":"Gerardo","family":"Cazzato","sequence":"additional","affiliation":[{"name":"Section of Molecular Pathology, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Lentini","sequence":"additional","affiliation":[{"name":"Department of Human Pathology of Adults and Developmental Age \u201cGaetano Barresi\u201d, Division of Pathology, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1001\/archderm.1972.01620040075020","article-title":"Trabecular carcinoma of the skin","volume":"105","author":"Toker","year":"1972","journal-title":"Arch. 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