各类感染疾病的致病因子包括细菌。然而，一些细菌种类的抗肿瘤效应引起了许多科学家的关注。人类口腔中栖息着丰富多样的细菌群落，其中一些细菌群落可能在抑制肿瘤方面具有重要作用。因此，寻找对口腔癌具有抗肿瘤活性的口腔细菌种类至关重要。本研究发现，牙龈卟啉单胞菌（Porphyromonas gingivalis），一种厌氧牙周病原菌，在肿瘤微环境（TME）中的高丰度与口腔鳞状细胞癌（OSCC）患者的长期生存呈正相关。体外实验证实了牙龈卟啉单胞菌通过诱导细胞周期在G2/M阶段的停滞加速口腔鳞状细胞癌细胞的死亡，从而发挥其抗肿瘤效应。我们还发现，牙龈卟啉单胞菌明显减少了4-硝基喹啉-1-氧的诱导性原位口腔鳞状细胞癌小鼠模型的肿瘤生长。转录组数据表明，牙龈卟啉单胞菌抑制了黏液O糖和其他O-糖的生物合成，以及趋化因子的表达。验证实验进一步证实了牙龈卟啉单胞菌处理能够降低黏液-1（MUC1）和C-X-C蛋白激素17（CXCL17）的表达。流式细胞术分析表明，牙龈卟啉单胞菌成功逆转了免疫抑制性TME，从而抑制了口腔鳞状细胞癌的生长。总之，本研究的发现表明，合理应用牙龈卟啉单胞菌可能成为口腔鳞状细胞癌的一种有前景的治疗策略。本文受版权保护，所有权利已被保留。

Bacteria are the causative agents of various infectious diseases; however, the anti-tumor effect of some bacterial species has attracted the attention of many scientists. The human oral cavity is inhabited by abundant and diverse bacterial communities, and some of these bacterial communities could play a role in tumor suppression. Therefore, it is crucial to find oral bacterial species that show anti-tumor activity on oral cancers. In the present study, we found that a high abundance of Porphyromonas gingivalis, an anaerobic periodontal pathogen, in the tumor microenvironment (TME) was positively associated with the longer survival of patients with oral squamous cell carcinoma (OSCC). An in vitro assay confirmed that P. gingivalis accelerated the death of OSCC cells by inducing cell cycle arrest at the G2/M phase, thus exerting its anti-tumor effect. We also found that P. gingivalis significantly decreased tumor growth in a 4-nitroquinoline-1-oxide-induced in situ OSCC mouse model. The transcriptomics data demonstrated that P. gingivalis suppressed the biosynthesis of mucin O-glycan and other O-glycans, as well as the expression of chemokines. Validation experiments further confirmed the downregulation of mucin-1 (MUC1) and C-X-C motif chemokine 17 (CXCL17) expression by P. gingivalis treatment. Flow cytometry analysis showed that P. gingivalis successfully reversed the immunosuppressive TME, thereby suppressing OSCC growth. In summary, the findings of the present study indicated that the rational use of P. gingivalis could serve as a promising therapeutic strategy for OSCC.This article is protected by copyright. All rights reserved.