Porphyromonas gingivalis promotes the malignant phenotype of oral squamous cell carcinoma through the recruitment of Treg cells.

Immunosuppression greatly drives oral squamous cell carcinoma (OSCC) progression and impairs patient prognosis, so exploring microbial regulators of the tumor immune microenvironment carries essential research value. While oral bacteria are tightly associated with worsening OSCC, it remains poorly understood how critical periodontal bacteria reshape immune cell composition to support tumor expansion. Here, we demonstrate that the common periodontal pathogen Porphyromonas gingivalis (P. gingivalis, P. g) stimulates cancer cells to secrete C-C motif chemokine ligand 20 (CCL20). This key signaling protein specifically recruits immunosuppressive regulatory T cells (Tregs). This bacterium elevates immune regulatory molecules, strengthens local immune suppression, and accelerates tumor growth in experimental OSCC models. Clinically, abundant P. gingivalis relates to advanced disease and poorly prognosis, and blocking C-C chemokine receptor type 6 (CCR6)-the immune cell receptor for CCL20-reverses the tumor-promoting effect. This study establishes a novel immune-mediated connection between periodontal infection and OSCC progression, and provides promising molecular targets to improve future prevention and targeted treatment for OSCC.