Periodontitis promotes tumor growth and immune evasion via PD-1/PD-L1.

BACKGROUND: Our study investigated the role of experimental periodontitis on tumor growth, local and systemic immunosuppressive status, and programmed death receptor 1 (PD-1) / programmed death ligand 1 (PD-L1) expression in oral squamous cell carcinoma (OSCC) and prostate cancer. METHODS: Mouse oral or prostate cancer xenograft models were divided into control, periodontitis and periodontitis + anti-PD-1 groups. Tumor volume and weight were recorded and the levels of relevant immune-suppressive cells and T cells were detected by flow cytometry or immunofluorescence. THP-1 cells were stimulated using conditioned media of LPS-stimulated Cal-27 cells and PD-L1 expression was measured by quantitative real-time PCR, western blotting and immunofluorescence. Tumor specimens from OSCC patients with or without periodontitis were also collected for immunofluorescence. RESULTS: Periodontitis significantly promoted tumor volume and weight. Compared to the control, the proportions of tumor-associated macrophages (TAMs), regulatory T cells (Tregs), PD-L1(+)TAMs and PD-1(+)CD8(+)T cells increased, while CD8(+)T cells decreased in the periodontitis group. Immunofluorescence demonstrated that there was an increase in PD-L1(+)TAMs and PD-1(+)CD8(+)T cells, but a decrease in IFN-gamma(+)CD8(+)T cells in both xenografts and clinical OSCC samples with periodontitis. In vitro, LPS-stimulated Cal-27 cells had a stronger potential to induce PD-L1 expression in macrophages compared with unstimulated Cal-27 cells. And the promoting effect of periodontitis on tumor growth and immune evasion was significantly attenuated after anti-PD-1 therapy. CONCLUSION: Periodontitis may facilitate tumor growth and immune escape evidenced by the increased immune-suppressive cells and the decreased functional T cells, via enhancing PD-1/PD-L1 expression in the tumor microenvironment.