{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T08:45:31Z","timestamp":1792226731883,"version":"4.4.0"},"reference-count":105,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Programmed death-ligand 1 (PD-L1) has become a central biomarker and therapeutic target across multiple solid tumors, yet its clinical meaning in prostate cancer (PCa) remains unsettled. PCa is commonly described as an immunologically \u2018cold\u2019 malignancy, characterized by limited baseline cytotoxic T-cell infiltration and a tumor microenvironment (TME) shaped by myeloid-driven suppression and low neoantigen load in many cases. Against this background, PD-L1 expression in PCa is typically low in untreated primary tumors but can increase in aggressive variants, advanced stages, and metastatic castration-resistant disease, where therapy pressure and microenvironmental cues may select for immune-evasive phenotypes. The literature is further complicated by major analytic variability, including differences in antibody clones and platforms, scoring algorithms (tumor proportion score, combined positive score, immune-cell scoring), cut-offs, tissue sites and timing, and pre-analytical variables such as fixation and decalcification. Collectively, available studies suggest that higher PD-L1 expression tends to be associated with adverse clinicopathological features and may enrich for responses to immune checkpoint inhibitors in selected settings, but PD-L1 immunohistochemistry alone is insufficient as a stand-alone predictive tool in unselected patients. This review synthesizes the biological drivers of PD-L1 regulation in PCa, dissects key methodological sources of heterogeneity in PD-L1 assessment, summarizes clinicopathological and therapeutic correlations, and outlines emerging biomarkers and approaches (including mismatch repair deficiency\/microsatellite instability, tumor mutational burden, gene-expression signatures, liquid biopsies, and neuro-immune interactions) that may enable more actionable patient stratification.<\/jats:p>","DOI":"10.3390\/ijms27041797","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T10:52:21Z","timestamp":1770979941000},"page":"1797","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["PD-L1 Expression in Prostate Cancer: Anatomopathological Features, Methodological Pitfalls, and Therapeutic Potential"],"prefix":"10.3390","volume":"27","author":[{"given":"Ludovica","family":"Pepe","sequence":"first","affiliation":[{"name":"Anatomic Pathology Unit, Department of Human Pathology in Adult and Developmental Age \u201cGaetano Barresi\u201d, University of Messina, 98125 Messina, Italy"},{"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Pizzimenti","sequence":"additional","affiliation":[{"name":"Anatomic Pathology Unit, Papardo Hospital, 98158 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4957-3283","authenticated-orcid":false,"given":"Pietro","family":"Tralongo","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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3478-9217","authenticated-orcid":false,"given":"Valeria","family":"Zuccal\u00e0","sequence":"additional","affiliation":[{"name":"Anatomic Pathology Unit, Department of Human Pathology in Adult and Developmental Age \u201cGaetano Barresi\u201d, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Ieni","sequence":"additional","affiliation":[{"name":"Anatomic Pathology Unit, Department of Human Pathology in Adult and Developmental Age \u201cGaetano Barresi\u201d, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Pepe","sequence":"additional","affiliation":[{"name":"Urology Unit, Cannizzaro Hospital, 95126 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1349-0910","authenticated-orcid":false,"given":"Gabriele","family":"Ricciardi","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":"Istituto Clinico Polispecialistico C.O.T. 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