Dept. of Periodontology, Justus-Liebig University, Giessen, Germany.
Dept. of Orthodontics, Justus-Liebig University, Giessen, Germany.
Front Cell Infect Microbiol. 2022 Jun 29;12:935806. doi: 10.3389/fcimb.2022.935806. eCollection 2022.
Chronic inflammation is known to contribute to various human cancers. (), is a gram-negative oral keystone pathogen that may cause severe periodontitis and expresses several virulence factors to affect the host immune system. Periodontitis is a chronic infectious disease that while progression, may cause loss of attachment and destruction of the tooth supporting tissues. Prostate cancer is one of the most common malignancies in men. Increasing evidence links periodontitis with prostate cancer, however the mechanisms explaining this relationship remain unclear. The aim of this study was to investigate the expression and signaling pathway of programmed death ligand 1 (PD-L1) in a prostate cancer cell line after infection with . and stimulation with . components 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 and treated with different concentrations of heat-killed and cell components, including the total membrane fraction, inner membrane fraction, outer membrane fraction, cytosolic fraction and peptidoglycan (PGN). Chemical inhibitors were used to block different important molecules of signaling pathways to assess the participating signal transduction mechanisms. PD-L1 expression was detected by Western blot after 24 h of infection. PD-L1 was demonstrated to be upregulated in prostate cancer cells after infection with viable and with heat-killed membrane fractions. Also isolated PGN induced PD-L1 up-regulation. The upregulation was mediated by the NOD1/NOD2 signaling pathway. No upregulation could be detected after treatment of the cells with lipopolysaccharide (LPS). These results indicate, that chronic inflammatory disease can contribute to tumor immune evasion by modifying the tumor microenvironment. Thus, chronic infection possibly plays an essential role in the immune response and may promote the development and progression of prostate cancer.
慢性炎症已知会导致多种人类癌症。（）是一种革兰氏阴性口腔关键病原体，可能导致严重的牙周炎，并表达几种毒力因子来影响宿主免疫系统。牙周炎是一种慢性传染病，随着疾病的进展，可能导致附着丧失和牙齿支持组织的破坏。前列腺癌是男性最常见的恶性肿瘤之一。越来越多的证据将牙周炎与前列腺癌联系起来，然而，解释这种关系的机制尚不清楚。本研究旨在研究前列腺癌细胞系感染后程序性死亡配体 1 (PD-L1) 的表达和信号通路。（）并刺激。（）成分，以揭示与细菌感染相关的肿瘤诱导免疫逃避的机制在肿瘤环境中。将不同浓度的活。（）感染前列腺癌细胞，并分别用不同浓度的热灭活。（）和细胞成分（包括全膜部分、内膜部分、外膜部分、胞质部分和肽聚糖（PGN））处理。用化学抑制剂阻断信号通路的不同重要分子，以评估参与的信号转导机制。感染 24 小时后通过 Western blot 检测 PD-L1 的表达。结果显示，活。（）感染和热灭活。（）膜部分均可上调前列腺癌细胞中的 PD-L1。分离的 PGN 也诱导 PD-L1 上调。这种上调是由 NOD1/NOD2 信号通路介导的。用细胞处理后未检测到 LPS。这些结果表明，慢性炎症性疾病可以通过改变肿瘤微环境来促进肿瘤免疫逃避。因此，慢性感染可能在免疫反应中发挥重要作用，并可能促进前列腺癌的发展和进展。
