西湖大学蔡尚课题组宣布他们的最新研究探明了由细菌-癌细胞结合决定的不同肿瘤免疫。2026年2月4日出版的《细胞》发表了这项成果。

在PyMT乳腺肿瘤中，该研究团队发现细胞内细菌，当驻留在癌细胞细胞质中时，通过触发胞质双链DNA （dsDNA）积累来促进转移，这反过来激活肿瘤固有的cGAS-STING-白细胞介素(IL)-17B途径，并将中性粒细胞重定向到抑制细胞毒性T细胞的肿瘤表型。相比之下，同一菌株的细菌，当存在于细胞外时，诱导抗肿瘤中性粒细胞活性而不参与STING途径。

生理上，在临床前模型中，消除细胞内细菌，或治疗性地引入细胞外细菌成分，消除免疫抑制并防止手术后转移性复发。在临床上，课题组人员发现的细菌入侵特征与乳腺癌患者的不良预后有关。总之，转移性壁龛中细菌和宿主细胞之间的空间相互作用可以形成不同的肿瘤免疫，强调细菌-宿主参与是癌症免疫调节的关键决定因素和潜在的治疗靶点。

据介绍，肿瘤内细菌代表了癌症生态系统中一个未被充分研究但有影响力的组成部分，对癌症的进展有着关键的影响。

附：英文原文

Title: Divergent tumor immunity determined by bacteria-cancer cell engagement

Author: Bingqing Yao, Xiaoqin Liu, Kanghui Ruan, Xiunan Fang, Chuhan Jiang, Weixiang Bian, Yajing Guo, Xiaosheng Zhu, Zebin Shang, Tianen Hu, Pei Cai, Meizhen Lin, Chunhui Wang, Xiaoyu Kuang, Fanglin Luo, Zhanhao Zhang, Shang Li, Jia Yao, Xu Li, Shang Cai

Issue&Volume: 2026-02-04

Abstract: Intratumor bacteria represent an understudied yet influential component of the cancer ecosystem, critically impinging cancer progression. In PyMT breast tumors, we find intracellular bacteria, when residing in cancer cell cytosol, promote metastasis by triggering cytosolic double-stranded DNA (dsDNA) accumulation, which in turn activates the tumor intrinsic cGAS-STING-interleukin (IL)-17B pathway and redirects neutrophils toward a protumor phenotype that inhibits cytotoxic T cells. By contrast, the same strain of bacteria, when present extracellularly, induces antitumor neutrophil activity without engaging the STING pathway. Physiologically, eliminating intracellular bacteria, or therapeutically introducing extracellular bacteria components, abrogates immunosuppression and prevents postsurgical metastatic recurrence in preclinical models. Clinically, the bacteria invasion signature we have developed is associated with poor prognosis in patients with breast cancer. In summary, the spatial interplay between bacteria and host cells in metastatic niches can shape divergent tumor immunity, highlighting bacterial-host engagement as a crucial determinant of cancer immune regulation and a potential therapeutic target.

DOI: 10.1016/j.cell.2025.12.044

Source: https://www.cell.com/cell/abstract/S0092-8674(25)01493-X