Mechanism of Porphyromonas gingivalis in establishing an immunosuppressive microenvironment in oral squamous cell carcinoma via the CCL20-CCR6 axis

doi:10.19438/j.cjoms.2025.06.002

Abstract

Abstract: PURPOSE: To explore the molecular mechanism by which Porphyromonas gingivalis(P. gingivalis) forms an immunosuppressive microenvironment in oral squamous cell carcinoma(OSCC) through the CCL20-CCR6 pathway. METHODS: Mouse-derived squamous cell carcinoma cell line SCC7 and P. gingivalis were cultured in vitro, and C57BL/6 mice were used to establish a tumor mouse model. Based on the infection status of P.gingivalis and the inhibition of the CCL20-CCR6 axis, C57BL/6 mice were divided into control group(SCC7), experimental group(SCC7+P.g), and intervention group(SCC7+P.g+CCR6 antagonist). The changes in tumor mass and volume among different groups were observed macroscopically, immunohistochemistry was used to detect CD4, FOXP3, PD-1, CTLA-4, LAG3, TIM3 and TIGIT in tumor tissues, ELISA was applied to measure the serum TGF-β levels. RESULTS: Compared to the control group, P.gingivalis infection in the experimental group significantly promoted the tumor tissue volume in OSCC-bearing mice(P<0.05), and the expression of CD4, Foxp3, CTLA-4, LAG3, TIM3, TIGIT, and TGF-β in the tumor tissue immunological microenvironment was significantly increased (P<0.05), while PD-1 expression showed no significant difference (P>0.05). The intervention group showed a reduction in tumor tissue volume compared to the experimental group (P<0.05), the expression of relevant immunosuppressive molecules and immune checkpoints CD4, Foxp3, PD-1, CTLA-4, LAG3, TIGIT, and TGF-β decreased(P<0.05), while TIM3 expression showed no significant difference(P>0.05). CONCLUSIONS: P.gingivalis recruits more Treg cells through the CCL20-CCR6 axis, regulates the expression of tumor-associated suppressive cytokines and immunosuppressive checkpoints, thereby promoting the formation of an immunosuppressive microenvironment in OSCC.

Key words: Porphyromonas gingivalis, Oral squamous cell carcinoma, Immunosuppressive microenvironment, Regulatory T cells, CCL20-CCR6

CLC Number:

R739.81

Naijibai·Momin, Xu Liming, Zhang Yibo, Li Jiaoyang, Liu Langqing, Ling Bin. Mechanism of Porphyromonas gingivalis in establishing an immunosuppressive microenvironment in oral squamous cell carcinoma via the CCL20-CCR6 axis[J]. China Journal of Oral and Maxillofacial Surgery, 2025, 23(6): 546-552.

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