RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
益生菌介导的肿瘤微环境重编程联合蛋白酶敏感型白细胞介素-15 和光热治疗
英文原题：Probiotic-mediated tumor microenvironment reprogramming with protease-sensitive interleukin-15 and photothermal therapy.
查看英文原题
Probiotic-mediated tumor microenvironment reprogramming with protease-sensitive interleukin-15 and photothermal therapy.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
中文摘要
T细胞功能不足或耗竭常导致基于免疫检查点阻断（ICB）的免疫治疗失败。白细胞介素-15（IL-15）已被用于预激活肿瘤微环境（TME）以提升免疫治疗效率。然而，其临床应用受到全身毒性和瘤内浓度低的限制。在此，我们工程化改造益生菌大肠杆菌Nissle 1917以递送IL-15和croconium染料，实现TME响应性释放IL-15并通过光热治疗放大抗肿瘤效应。这促进了抗原呈递细胞和T细胞的募集，以及IL-15诱导的T/NK 细胞的扩增。因此，它阻止了肿瘤生长并诱导了全身性记忆T细胞的产生。该方法与ICB联合在多种免疫热肿瘤和免疫冷肿瘤中产生了显著的协同效应。本研究提供了一种细胞因子靶向递送策略，展示了其与免疫原性细胞死亡诱导剂联合用于TME重编程的高度潜力。
展开英文摘要原文
T cell inadequacy or exhaustion often causes the failure of immune checkpoint blockade (ICB)-based immunotherapy. Interleukin-15 (IL-15) has been used to prime the tumor microenvironment (TME) to boost the efficiency of immunotherapy.
However, its clinical application is hindered by systemic toxicity and low intratumoral concentrations.
Here, we engineer the probiotic Escherichia coli Nissle 1917 to deliver IL-15 and croconium dye, enabling the TME-responsive release of IL-15 and amplifying the antitumor effect through photothermal therapy. This promotes the recruitment of antigen-presenting cells and T cells and the expansion of T/natural killer cells induced by IL-15. Consequently, it halts the tumor growth and induces systemic memory T cell production. This approach combined with ICBs generates prominent synergistic effects across various immune-hot and immune-cold tumors.
This study provides a strategy for targeted delivery of cytokines, demonstrating its high potential for TME reprogramming when combined with immunogenic cell death inducers.
论文信息
- 作者
- Wang H、Zheng L、Yang C、Jia L、Zhou R、Liu H、Dong Y、Xu X
- 第一作者单位
- Department of Critical Care Medicine, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital (The First Affiliated Hospital, Southern University of Science and Technology, The Second Clinical Medical College, Jinan University), Shenzhen, Guangdong 518020, China.China
- 通讯作者单位
- Department of Critical Care Medicine, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital (The First Affiliated Hospital, Southern University of Science and Technology, The Second Clinical Medical College, Jinan University), Shenzhen, Guangdong 518020, China; Center for Drug Research and Development, Guangdong Provincial Key Laboratory for Research and Evaluation of Pharmaceutical Preparations, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, China; State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China; State Key Laboratory of Antiviral Drugs, School of Pharmacy, Henan University, Kaifeng 475004, China. Electronic address: jgwang@icmm.ac.cn.China
- 期刊
- Cell reports. Medicine2025 Jun 17
- 原文标识
- PubMed 40532661 · DOI 10.1016/j.xcrm.2025.102191
在 PubMed 查看 → 出版商原文（DOI） 全文 PDF（PMC）· 可下载 治疗专题与资料阅读指南 资料来源与翻译说明 报告译文或资料问题 →