细菌因其独特的能力而成为理想的抗癌剂和载体，可方便地进行基因操作、肿瘤特异性靶向和深层组织渗透。然而，细菌介导的癌症治疗（BMCT）的具体分子机制尚未阐明。在本研究中，我们发现TLR4信号通路对于沙门氏菌介导的肿瘤靶向、肿瘤抑制以及肝脾保护至关重要。小鼠中 TLR4 敲除降低了沙门氏菌治疗后肿瘤微环境 (TME) 中细胞因子和趋化因子的水平，例如 S100a8、S100a9、TNF-α 和 IL-1β，从而抑制了肿瘤细胞死亡和营养物质释放，从而导致细菌减少肿瘤中的含量并以负反馈方式减弱抗肿瘤功效。重要的是，我们发现 S100a8 和 S100a9 在沙门氏菌介导的癌症治疗 (SMCT) 中发挥主导作用。当用特定抑制剂阻断时，抗肿瘤功效被消除，肝损伤也很明显。这些发现阐明了沙门氏菌介导的肿瘤靶向、抑制和宿主抗菌防御的机制，为临床癌症治疗提供了见解。© 2024 UICC。

Bacteria are ideal anticancer agents and carriers due to their unique capabilities that are convenient in genetic manipulation, tumor-specific targeting, and deep-tissue penetration. However, the specific molecular mechanisms of bacteria-mediated cancer therapy (BMCT) have not been clarified. In this study, we found that TLR4 signaling pathway is critical for Salmonella-mediated tumor targeting, tumor suppression, and liver and spleen protection. TLR4 knockout in mice decreased the levels of cytokines and chemokines, such as S100a8, S100a9, TNF-α, and IL-1β, in tumor microenvironments (TMEs) after Salmonella treatment, which inhibited tumor cell death and nutrient release, led to reduced bacterial contents in tumors and attenuated antitumor efficacy in a negative feedback manner. Importantly, we found that S100a8 and S100a9 played a leading role in Salmonella-mediated cancer therapy (SMCT). The antitumor efficacy was abrogated and liver damage was prominent when blocked with a specific inhibitor. These findings elucidated the mechanism of Salmonella-mediated tumor targeting, suppression, and host antibacterial defense, providing insights into clinical cancer therapeutics.© 2024 UICC.