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治疗性细菌训练的 NK 细胞赋予针对癌症转移的长期保护

英文原题：Therapeutic bacteria-trained NK cells confer long-term protection against cancer metastasis.

查看英文原题

Therapeutic bacteria-trained NK cells confer long-term protection against cancer metastasis.

PubMed 2026/06/03（内容时间） Mol Ther Q1 · IF 11.4（JCR 2025）

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技术：NK 细胞地区：中国
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中文摘要

转移导致90%的癌症相关死亡，然而预防策略仍然有限。在此，我们报道单剂治疗性沙门氏菌——一种重要的抗肿瘤细菌疗法——通过诱导“训练”自然杀伤（NK）细胞，为小鼠提供针对转移的持久保护。整合功能和多组学分析揭示，沙门氏菌训练的NK（stNK）细胞建立起一种持久重编程的表观基因组，其特征是增强的促生存信号和免疫效应功能，从而在二次刺激时产生更强的IFN-γ释放和细胞毒性。我们进一步表明，这种训练需要IL-12的短暂脉冲与持续的IL-18信号相结合。至关重要的是，stNK细胞在预防转移方面显著优于常规免疫检查点疗法，包括PD-1和TIGIT阻断，突显了对抗转移的独特免疫学机制。这些发现凸显了细菌癌症疫苗或训练NK细胞作为预防转移有效策略的潜力。

展开英文摘要原文

Metastasis causes 90% of cancer-related deaths, yet preventive strategies remain limited.

Here, we report that a single dose of therapeutic Salmonella, a prominent anti-tumor bacterial therapy, provides long-lasting protection against metastasis in mice by inducing "trained" natural killer (NK) cells. Integrated functional and multi-omics analyses revealed that Salmonella-trained NK (stNK) cells establish an enduring reprogrammed epigenome characterized by enhanced pro-survival signaling and immune effector functions, resulting in more potent IFN-γ release and cytotoxicity upon secondary stimulation.

We further showed that this training requires a transient pulse of IL-12 combined with sustained IL-18 signaling. Crucially, stNK cells significantly outperform conventional immune checkpoint therapies, including PD-1 and TIGIT blockade, in preventing metastasis, underscoring the unique immunological mechanisms in combating metastasis.

These findings highlight the potential of bacterial cancer vaccines or trained NK cells as effective strategies for metastasis prevention.

论文信息

作者
Rong L、Hu J、Jin W、Li R、Wu Y、Zhou N、Zhao X、Zhou Z
第一作者单位
State Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China. Electronic address: li.rong@siat.ac.cn.China
通讯作者单位
State Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China; Shenzhen Key Laboratory for Cancer Metastasis and Personalized Therapy, Department of Clinical Oncology, The University of Hong Kong-Shenzhen Hospital, Shenzhen 518053, China; Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen University, Guangzhou 510120, China; Materials Innovation Institute for Life Sciences and Energy (MILES), HKU-SIRI, Shenzhen, P.R. China. Electronic address: jdhuang@hku.hk.China
期刊
Molecular therapy : the journal of the American Society of Gene Therapy2026 Aug 5
原文标识
PubMed 42237539　·　DOI 10.1016/j.ymthe.2026.05.023

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