{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T05:02:52Z","timestamp":1785301372184,"version":"3.55.0"},"reference-count":65,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"\n Purpose<\/jats:title>\n \n This study investigates the relationship between\n Porphyromonas gingivalis<\/jats:italic>\n (\n P. gingivalis<\/jats:italic>\n ) infection status and preoperative levels of inflammatory markers in peripheral blood as well as the tumor immune microenvironment (TIME) in patients with oral squamous cell carcinoma (OSCC).\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n This retrospective study enrolled 201 patients with oral squamous cell carcinoma (OSCC) and collected their relevant clinical data, preoperative peripheral blood samples, and histopathological sections. Immunohistochemical analysis was performed to assess\n P. gingivalis<\/jats:italic>\n expression levels in the patients\u2019 tissue samples, and the patients were divided into high-expression and low-expression groups. First, we analyzed the relationships between clinical indicators\u2014such as tumor stage and pathological grade\u2014and\n P. gingivalis<\/jats:italic>\n expression levels. Additionally, systemic inflammation markers, including the systemic immune\u2013inflammation index (SII), the neutrophil\u2013lymphocyte ratio (NLR), the platelet\u2013lymphocyte ratio (PLR), and the systemic inflammatory response index (SIRI), were calculated on the basis of peripheral blood test results; we analyzed the correlations of these variables with clinical indicators and\n P. gingivalis<\/jats:italic>\n expression levels. At the same time, immunohistochemical analysis was performed on OSCC tissue samples to assess the abundance of CD4+ T cells and the expression of chemokine ligand 20 (CCL20), chemokine receptor 6 (CCR6), interleukin 10 (IL-10), FOXP3, and LAG-3 in OSCC tissue samples to assess the relationship between\n P. gingivalis<\/jats:italic>\n expression levels and systemic inflammatory markers in peripheral blood as well as the local immunosuppressive microenvironment.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Patients with higher\n P. gingivalis<\/jats:italic>\n expression levels in tumor tissue had lower tumor differentiation (\n P<\/jats:italic>\n \u00a0&lt;\u00a00.001) and shorter survival times (\n P<\/jats:italic>\n \u00a0&lt;\u00a00.001). Two systemic inflammatory markers\u2014the SII and SIRI\u2014were associated with tumor differentiation (SII:\n P<\/jats:italic>\n \u00a0=\u00a00.020; SIRI:\n P<\/jats:italic>\n \u00a0=\u00a00.004), while the SII, NLR, PLR, and SIRI were associated with the T stage (SII:\n P<\/jats:italic>\n \u00a0&lt;\u00a00.001; NLR:\n P<\/jats:italic>\n \u00a0=\u00a00.003; PLR:\n P<\/jats:italic>\n \u00a0=\u00a00.017; SIRI:\n P<\/jats:italic>\n \u00a0=\u00a00.003); the SII and PLR were associated with the N stage (SII:\n P<\/jats:italic>\n \u00a0=\u00a00.002; PLR:\n P<\/jats:italic>\n \u00a0=\u00a00.046). The NLR and SIRI were associated with\n P. gingivalis<\/jats:italic>\n expression levels (NLR:\n P<\/jats:italic>\n \u00a0=\u00a00.026; SIRI:\n P<\/jats:italic>\n \u00a0=\u00a00.021). Multivariate logistic regression analysis revealed that pT stage is an independent risk factor for high expression of\n P. gingivalis<\/jats:italic>\n , exhibiting a dose-response relationship (pT2: OR\u00a0=\u00a05.83, pT3: OR\u00a0=\u00a011.69, pT4: OR\u00a0=\u00a043.66; all\n P<\/jats:italic>\n \u00a0&lt;\u00a00.01); poorly differentiated tumors (OR\u00a0=\u00a011.02) and lip cancer (OR\u00a0=\u00a00.27) were also independent risk factors (\n P<\/jats:italic>\n \u00a0&lt;\u00a00.05). Immunohistochemical results revealed that OSCC patients with higher\n P. gingivalis<\/jats:italic>\n levels had significantly higher positive expression of CD4, FOXP3, LAG3, CCR6, CCL20, and IL-10 (CD4, FOXP3, LAG3, CCR6, IL-10:\n P<\/jats:italic>\n \u00a0&lt;\u00a00.0001; CCL20:\n P<\/jats:italic>\n \u00a0=\u00a00.0006). Four systemic inflammation markers\u2014the SII, NLR, PLR, and SIRI\u2014were associated with the expression levels of FOXP3, CCR6, CCL20, and IL-10 in OSCC tumor tissues (\n P<\/jats:italic>\n \u00a0&lt;\u00a00.05); among these markers, the SII and PLR were significantly associated with LAG3 expression levels (\n P<\/jats:italic>\n \u00a0&lt;\u00a00.05). Furthermore, only SIRI values were associated with CD4 expression levels (\n P<\/jats:italic>\n \u00a0&lt;\u00a00.05).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n P. gingivalis<\/jats:italic>\n alters the local immune status by modulating key immune molecules\u2014CD4, FOXP3, CCL20, CCR6, LAG-3, and IL-10\u2014in the OSCC tumor microenvironment. These local changes are significantly associated with systemic inflammation levels, indicating a close interaction between the local immune microenvironment and systemic inflammatory responses, both of which contribute to the development and progression of OSCC.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fonc.2026.1747849","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T04:36:46Z","timestamp":1785299806000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A study on the correlation between systemic inflammatory markers in the local tumor immune microenvironment and Porphyromonas gingivalis infection status in patients with oral squamous cell carcinoma"],"prefix":"10.3389","volume":"16","author":[{"given":"Jie","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Oncology Surgery, The First Affiliated Hospital (Affiliated 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China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Ling","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Oncology Surgery, The First Affiliated Hospital (Affiliated Stomatological Hospital) of Xinjiang Medical University","place":["Urumqi, China"]},{"name":"Institute of Stomatology, Xinjiang Uygur Autonomous Region","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1007\/978-3-032-04734-2_1","article-title":"Preventive measures in oral cancer: an overview","volume":"107","author":"D'souza","year":"2018","journal-title":"BioMed Pharmacother"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19840201)53:3<563::aid-cncr2820530332>3.0.co;2-f","article-title":"Oral leukoplakia and Malignant transformation. a follow-up study 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