Key Points P. gingivalis inhibited macrophage attack on OSCC cells. P. gingivalis promoted the polarization of macrophages into M2 TAMs. P. gingivalis upregulated the expression of protumor molecules. Visual Abstract The relationship of Porphyromonas gingivalis and oral squamous cell carcinoma (OSCC) has been studied for several years. Previous studies have focused on the direct effect of P. gingivalis on the activities of primary epithelial cells and OSCC cells. However, the immune system is responsible for mediating cancer development, whether P. gingivalis can affect oral cancer immunity has seldom been explored to date. In this study, we investigated the role of P. gingivalis in the immunoevasion of OSCC. We evaluated the effect of P. gingivalis on the phagocytosis of Cal-27 cells (OSCC cell line) by bone marrow–derived macrophages in vitro and studied the effect of P. gingivalis on the growth of OSCC and the polarization of tumor-associated macrophages in vivo. We found that P. gingivalis was able to inhibit the phagocytosis of Cal-27 cells by macrophages, and membrane-component molecules of P. gingivalis, such as proteins, were speculated to be the effector components. In addition, sustained infection with antibiotics-inactivated P. gingivalis promoted OSCC growth in mice and induced the polarization of macrophages into M2 tumor-associated macrophages, which mainly display protumor properties. Transcriptome analysis and quantitative RT-PCR revealed that P. gingivalis infection upregulated the expression of genes encoding protumor molecules in Cal-27 cells (suprabasin, IL-1R2, and CD47) and in macrophages (IL-1α, CCL-3, and CCL-5). Our in vitro and in vivo data suggest that P. gingivalis can promote immunoevasion of oral cancer by protecting cancer from macrophage attack. To our knowledge, the present study reveals a novel mechanism by which P. gingivalis promotes OSCC development.

中文翻译：

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牙龈卟啉单胞菌通过保护癌症免受巨噬细胞攻击来促进口腔癌的免疫逃避

要点 P. gingivalis 抑制巨噬细胞对 OSCC 细胞的攻击。P. gingivalis 促进巨噬细胞极化为 M2 TAM。P. gingivalis 上调了原肿瘤分子的表达。视觉摘要 牙龈卟啉单胞菌与口腔鳞状细胞癌 (OSCC) 的关系已被研究多年。以前的研究集中在 P. gingivalis 对原代上皮细胞和 OSCC 细胞活性的直接影响。然而，免疫系统负责介导癌症的发展，牙龈卟啉单胞菌是否会影响口腔癌免疫迄今为止很少被探索。在这项研究中，我们调查了牙龈卟啉单胞菌在 OSCC 免疫逃避中的作用。我们评估了 P 的影响。gingivalis 对体外骨髓来源的巨噬细胞对 Cal-27 细胞（OSCC 细胞系）的吞噬作用，并研究了 P. gingivalis 对 OSCC 生长和体内肿瘤相关巨噬细胞极化的影响。我们发现P. gingivalis 能够抑制巨噬细胞对Cal-27 细胞的吞噬作用，推测P. gingivalis 的膜成分分子，如蛋白质，是效应成分。此外，抗生素灭活的牙龈卟啉单胞菌持续感染促进了小鼠 OSCC 的生长，并诱导巨噬细胞极化为 M2 肿瘤相关巨噬细胞，主要表现出促肿瘤特性。转录组分析和定量 RT-PCR 显示，牙龈卟啉单胞菌感染上调 Cal-27 细胞（suprabasin、IL-1R2、CD47）和巨噬细胞（IL-1α、CCL-3 和 CCL-5）。我们的体外和体内数据表明，牙龈卟啉单胞菌可以通过保护癌症免受巨噬细胞攻击来促进口腔癌的免疫逃避。据我们所知，本研究揭示了牙龈卟啉单胞菌促进 OSCC 发展的新机制。