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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Tumor-associated macrophages are key components of the tumor microenvironment in oral carcinogenesis; however, their role is not yet fully understood. We aimed to characterize the expression of macrophage (M) markers across the spectrum of oral carcinogenesis, including oral leukoplakias (OL) and oral squamous cell carcinomas (OSCCs). This immunohistochemical study analyzed the macrophage density (cells\/mm2) based on the expression of CD68 (pan-macrophage), CD163 (M2), and CD80 (M1) in 81 samples, including healthy mucosa (n = 16), OL (n = 30), and OSCC (n = 35), in both epithelial and subepithelial compartments. All markers showed a progressive increase across the study groups, with significantly higher densities in OSCC than in healthy mucosa (p &lt; 0.001), consistently higher in the subepithelial compartment. CD163 was the most expressed marker (increasing from 78.96 cells\/mm2 in healthy mucosa to 300.56 cells\/mm2 in OSCC), whereas CD80 was the least abundant, particularly in OSCC (35.66 cells\/mm2 in healthy tissue to 188.49 cells\/mm2 in OSCC). No significant associations were observed between biomarker expression and clinicopathological variables. These results support the involvement of macrophages during oral carcinogenesis, particularly CD163+ (M2) cells, and highlight the potential prognostic and therapeutic relevance of these markers.<\/jats:p>","DOI":"10.3390\/ijms27156889","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T12:57:56Z","timestamp":1785761876000},"page":"6889","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immunophenotypic Characterization of Tumor-Associated Macrophages in Oral Carcinogenesis: An Observational Study"],"prefix":"10.3390","volume":"27","author":[{"given":"Mafalda","family":"Alves","sequence":"first","affiliation":[{"name":"UNIPRO-Oral Pathology and Rehabilitation Research Unit, IUCS-CESPU, University Institute of Health Sciences, 4585-116 Gandra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0845-2944","authenticated-orcid":false,"given":"Sara","family":"Ferreira","sequence":"additional","affiliation":[{"name":"UNIPRO-Oral Pathology and Rehabilitation Research Unit, IUCS-CESPU, University Institute of Health Sciences, 4585-116 Gandra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda","family":"Garc\u00eas","sequence":"additional","affiliation":[{"name":"UNIPRO-Oral Pathology and Rehabilitation Research Unit, IUCS-CESPU, University Institute of Health Sciences, 4585-116 Gandra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Esp\u00edndula","sequence":"additional","affiliation":[{"name":"UNIPRO-Oral Pathology and Rehabilitation Research Unit, IUCS-CESPU, University Institute of Health Sciences, 4585-116 Gandra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6693-4426","authenticated-orcid":false,"given":"Filomena","family":"Salazar","sequence":"additional","affiliation":[{"name":"UNIPRO-Oral Pathology and Rehabilitation Research Unit, IUCS-CESPU, University Institute of Health Sciences, 4585-116 Gandra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0423-0976","authenticated-orcid":false,"given":"Jos\u00e9 J\u00falio","family":"Pacheco","sequence":"additional","affiliation":[{"name":"UNIPRO-Oral Pathology and Rehabilitation Research Unit, IUCS-CESPU, University Institute of Health Sciences, 4585-116 Gandra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5349-1091","authenticated-orcid":false,"given":"M\u00e1rcio","family":"Diniz-Freitas","sequence":"additional","affiliation":[{"name":"Medical-Surgical Dentistry Research Group, Health Research Institute of Santiago de Compostela, School of Medicine and Dentistry, Santiago de Compostela University, 15703 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Lopes","sequence":"additional","affiliation":[{"name":"UNIPRO-Oral Pathology and Rehabilitation Research Unit, IUCS-CESPU, University Institute of Health Sciences, 4585-116 Gandra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saman","family":"Warnakulasuriya","sequence":"additional","affiliation":[{"name":"The WHO Collaborating Centre for Oral Cancer, King\u2019s College London, London SE1 9RT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4405-0240","authenticated-orcid":false,"given":"Leonor","family":"Delgado","sequence":"additional","affiliation":[{"name":"UNIPRO-Oral Pathology and Rehabilitation Research Unit, IUCS-CESPU, University Institute of Health Sciences, 4585-116 Gandra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8938-1297","authenticated-orcid":false,"given":"Luis","family":"Monteiro","sequence":"additional","affiliation":[{"name":"UNIPRO-Oral Pathology and Rehabilitation Research Unit, IUCS-CESPU, University Institute of Health Sciences, 4585-116 Gandra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1546","DOI":"10.1111\/odi.15265","article-title":"Tumour-Associated Macrophages in Oral Squamous Cell Carcinoma","volume":"31","author":"Chaurasia","year":"2025","journal-title":"Oral Dis."},{"key":"ref_2","first-page":"e70090","article-title":"Global cancer statistics 2024: GLOBOCAN estimates of incidence and mortality worldwide for 34 cancers in 186 countries","volume":"76","author":"Sung","year":"2026","journal-title":"CA Cancer J. 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