Prevotella Intermedia Drives Oral Squamous Cell Carcinoma Occurrence And Development

Objective To investigate the role of Prevotella intermedia (Pi) in oral mucosal carcinogenesis and its association with M2 macrophage-driven progression of oral squamous cell carcinoma (OSCC). Methods: Pi colonization was quantified in paraffin-embedded oral leukoplakia (OLK), OSCC, and healthy control (HC) tissues using species-specific fluorescence in situ hybridization (FISH). Immune microenvironment features were analyzed via multiplex immunofluorescence staining (CD68/CD163/IL-10/ISG15). ISG15-knockout (KO) and wild-type (WT) THP-1 macrophages were polarized by Pi and indirectly co-cultured with human oral keratinocytes (HOK) and CAL27 cancer cells to evaluate the effects of Pi-infected macrophage supernatants on epithelial cell proliferation and migration. Results: Pi abundance was significantly higher in OSCC tissues compared to OLK and HC tissues (P<0.05). Elevated CD163+/CD68+ ratios and co-localization of IL-10/ISG15 indicated increased M2 macrophage infiltration during OLK-to-OSCC progression. Pi-activated M2 macrophages promoted proliferation, migration, and invasion of CAL27 and HOK cells via ISG15-dependent mechanisms. ISG15 knockdown attenuated Pi-induced M2 polarization and suppressed malignant phenotypes in epithelial cells. Conclusions Pi drives OSCC progression through ISG15-mediated M2 macrophage polarization, facilitating epithelial cell malignant transformation and immunosuppressive microenvironment formation.