[Prophyromonas gingivalis Promotes the Formation of Immunosuppressive Microenvironment in Oral Squamous Cell Carcinoma by CCR6(+) Regulatory T Cells: A Study of the Mechanisms Invovled].

OBJECTIVE: To investigate the mechanisms by which Porphyromonas gingivalis (P. gingivalis) promotes the malignant progression of oral squamous cell carcinoma (OSCC) through the recruitment of chemokine receptor 6-positive (CCR6(+)) regulatory T cells (Treg) in the tumor microenvironment (TME). METHODS: The Cancer Genome Atlas (TCGA) database was used to analyze the correlation between chemokine ligand 20 (CCL20), CCR6, and Treg. The Treg enrichment index and the expression levels of interleukin (IL)-10 and tumor necrosis factor β1 (TGF-β1) were assessed in the high CCR6 expression group of OSCC patients. C57BL/6 mice were randomly assigned to a control group and an experimental group (n = 6 in each group). The control group received a single injection of 100 μL SCC7, a mice head and neck squamous carcinoma cell line, while the experimental group received a single injection of 100 μL mixture of SCC7 cells and P. gingivalis in the cheek. After two weeks, the mice were sacrificed, and immunohistochemistry was performed to assess the expression levels of CCR6 and forkhead box protein 3 (FOXP3) in OSCC. Flow cytometry was performed to analyze the effects of P. gingivalis on OSCC malignant biological behavior, CCR6(+) Treg cells, and the immune microenvironment. RESULTS: Bioinformatics analysis revealed a correlation between CCL20, CCR6, and Treg (r = 0.373, P < 0.000 1). OSCC patients with high CCR6 expression showed higher Treg enrichment scores and increased IL-10 expression. Animal experiments showed that P. gingivalis promoted the increase in the tumor volume (mm(3)) (0.294 ± 0.105 in the control group and 0.526 ± 0.101 in the experimental group, P < 0.01) and mass (mg) (206.200 ± 53.950 in the control group and 376.000 ± 119.200 in the experimental group, P < 0.01) in mice with OSCC. Immunohistochemistry confirmed a correlation between CCR6 and FOXP3 (r = 0.659, P < 0.05), and P. gingivalis promoted the expression of CCR6 and FOXP3. Flow cytometry analysis showed that P. gingivalis increased the proportion of CCR6(+) Treg (%) (13.780 ± 1.506 in the control group and 18.260 ± 2.257 in the experimental group, P < 0.01) and decreased the proportion of CD8(+) T cells (%) (27.120 ± 1.647 in the control group and 21.060 ± 3.148 in the experimental group, P < 0.01) in OSCC, thereby promoting the formation of a immunosuppressive microenvironment. CONCLUSION: P. gingivalis promotes the malignant progression of OSCC by recruiting CCR6(+) Treg cells to form an immunosuppressive TME.