{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:54:38Z","timestamp":1790747678581,"version":"4.1.0"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"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":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Accumulating evidence indicates that oral microbiota dysbiosis and periodontal pathogens contribute to the initiation and progression of oral squamous cell carcinoma (OSCC). However, the molecular mechanisms underlying the interaction between\n                      <jats:italic>Porphyromonas gingivalis<\/jats:italic>\n                      and the tumor immune microenvironment remain incompletely understood. This study aimed to investigate the potential role of a TLR4-associated ERK\/CD155\/TIGIT signaling pathway in\n                      <jats:italic>P. gingivalis<\/jats:italic>\n                      -mediated immunosuppressive microenvironment formation during OSCC progression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Genes associated with\n                      <jats:italic>P. gingivalis<\/jats:italic>\n                      and TIGIT were obtained from GeneCards and The Cancer Genome Atlas (TCGA) databases. Candidate hub genes were identified through bioinformatic analyses. An SCC7 syngeneic orthotopic transplantation mouse model was established, and SCC7 cells were injected together with\n                      <jats:italic>Porphyromonas gingivalis<\/jats:italic>\n                      . Tumor growth was assessed by measuring tumor volume and weight. Expression levels of TLR4, ERK1\/2, CD155, and TIGIT were evaluated by immunohistochemistry and quantitative real-time PCR (qRT-PCR). Flow cytometry was performed to analyze tumor-infiltrating immune-cell populations. The TLR4 inhibitor TAK-242 was used to investigate the involvement of TLR4-associated signaling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Bioinformatic analysis identified TLR4 as a biologically relevant candidate hub gene potentially linking\n                      <jats:italic>P. gingivalis<\/jats:italic>\n                      -associated signaling and TIGIT-related immune regulation. Exposure to\n                      <jats:italic>P. gingivalis<\/jats:italic>\n                      significantly promoted tumor growth and increased the expression of TLR4, ERK1\/2, CD155, and TIGIT in tumor tissues. Flow cytometric analysis revealed immune microenvironment remodeling characterized by increased proportions of CD4+ T cells, TIGIT-positive Tregs, and IL-10-positive cells, accompanied by reduced CD8+ T-cell infiltration and decreased frequencies of Ki67+CD8+ and CD44+CD8+ T cells. Treatment with the TLR4 inhibitor TAK-242 partially reversed these tumor-promoting, immunological, and molecular changes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our findings suggest that exposure to\n                      <jats:italic>P. gingivalis<\/jats:italic>\n                      may promote OSCC progression by contributing to immune microenvironment remodeling. Increased expression of TLR4, ERK1\/2, CD155, and TIGIT, together with the effects of TLR4 inhibition, supports the potential involvement of a TLR4-associated ERK\/CD155\/TIGIT signaling pathway in this process. However, the precise molecular mechanisms require further validation using genetic and functional approaches.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1773440","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:56:04Z","timestamp":1790744164000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Potential involvement of a TLR4-associated CD155\/TIGIT pathway in Porphyromonas gingivalis-induced immunosuppressive microenvironment formation in oral squamous cell carcinoma"],"prefix":"10.3389","volume":"16","author":[{"given":"Xiao","family":"Tian","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Oncology Surgery, First Affiliated Hospital of Xinjiang Medical University","place":["Urumqi, China"]},{"name":"Affiliated Stomatology Hospital, Institute of Stomatology, Xinjiang Uygur Autonomous 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Autonomous Region","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Wang","sequence":"additional","affiliation":[{"name":"Affiliated Stomatology Hospital, Institute of Stomatology, Xinjiang Uygur Autonomous Region","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Langqing","family":"Liu","sequence":"additional","affiliation":[{"name":"Affiliated Stomatology Hospital, Institute of Stomatology, Xinjiang Uygur Autonomous Region","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Ling","sequence":"additional","affiliation":[{"name":"Affiliated Stomatology Hospital, Institute of Stomatology, Xinjiang Uygur Autonomous Region","place":["Urumqi, 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