Porphyromonas gingivalis induces PD-L1 upregulation in prostate cancer cells : impact of the periodontopathogenic bacterium Porphyromonas gingivalis on prostate cancer cells

Abstract

Chronic inflammation is known to contribute to several human cancers. Porphyromonas gingivalis (P. gingivalis), a keystone gram-negative oral periodontopathogen leading to severe periodontitis, expresses virulence factors to impair the host immune system. This study investigated the expression and signaling pathway of programmed death ligand 1 (PD-L1) in a prostate cancer cell line after infection with P. gingivalis and treatment with isolated P. gingivalis fractions and peptidoglycan (PGN) to reveal the mechanism of tumor-induced immune evasion associated with bacterial infection in the tumor environment. Prostate cancer cells were infected with different concentrations of viable P. gingivalis and treated with different concentrations of heat-killed P. gingivalis and P. gingivalis cell fractions, including the cytosolic fraction, total membrane fraction, inner membrane fraction and outer membrane fraction. Chemical inhibitors were used to block different major components of signaling pathways in order to reveal the involved signal transduction mechanisms. PD-L1 expression was detected using Western blotting after 24 h of stimulation. PD-L1 expression was demonstrated to be upregulated in prostate cancer cells after infection with viable P. gingivalis and treatment with heat-killed P. gingivalis, P. gingivalis membrane fractions and isolated PGN. The upregulation was shown to be mediated by the NOD1/NOD2 signaling pathway. No upregulation was found upon stimulation with P. gingivalis lipopolysaccharide (LPS). The findings in vitro indicate that chronic inflammation may contribute to tumor immune evasion by modulating the tumor microenvironment. Thus, chronic infection may play an important role in the innate immune response and influence the development and progression of prostate cancer.