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
细胞因子诱导的记忆样 NK 细胞来源的小细胞外囊泡对实体瘤的治疗作用
英文原题：Therapeutic effect of small extracellular vesicles from cytokine-induced memory-like natural killer cells on solid tumors.
查看英文原题
Therapeutic effect of small extracellular vesicles from cytokine-induced memory-like natural killer cells on solid tumors.
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
源自多种自然杀伤（NK）细胞系的小细胞外囊泡（sEV）已证明具有卓越的抗肿瘤活性。然而，来自人原代NK细胞，尤其是记忆样NK细胞的sEV，很少被用于癌症治疗。在本研究中，我们从经IL-12、IL-15和IL-18培养的人记忆样NK细胞中获得了sEV（mNK-sEV），其表现出强大的细胞因子分泌能力。研究发现，mNK-sEV通过巨胞饮作用进入癌细胞，并通过caspase依赖性途径诱导细胞凋亡。与常规培养NK细胞来源的sEV（conNK-sEV）相比，mNK-sEV对肿瘤生长的抑制程度更大。同时，药代动力学和生物分布结果证实，在异种移植小鼠模型的肿瘤中，mNK-sEV的蓄积量高于conNK-sEV。值得注意的是，mNK-sEV中颗粒溶素（GNLY）含量的升高，至少部分可能有助于增强治疗效果。在此，我们的结果表明，mNK-sEV可以作为一种新型治疗试剂，用于有效的癌症治疗。
展开英文摘要原文
Small extracellular vesicles (sEV) derived from diverse natural killer (NK) cell lines have proven their exceptional antitumor activities.
However, sEV from human primary NK cells, especially memory-like NK cells, are rarely utilized for cancer treatment. In this study, we obtained sEV from IL-12, IL-15 and IL-18 cultured human memory-like NK cells (mNK-sEV) that showed strong cytokine-secretory ability. It was uncovered that mNK-sEV entered cancer cells via macropinocytosis and induced cell apoptosis via caspase-dependent pathway.
Compared to sEV from conventionally cultured NK cells (conNK-sEV), mNK-sEV inhibited tumor growth to a greater extent. Concomitantly, pharmacokinetics and biodistribution results validated a higher accumulation of mNK-sEV than conNK-sEV in tumors of xenografted murine models.
Notably, elevated containment of granulysin (GNLY) within mNK-sEV, at least in part, may contribute to the enhanced therapeutic effect.
Herein our results present that mNK-sEV can be a novel class of therapeutic reagent for effective cancer treatment.
论文信息
- 作者
- Shi Y、Chen Y、Wang Y、Mo D、Ai H、Zhang J、Guo M、Qian H
- 第一作者单位
- Jiangsu Province Key Laboratory of Medical Science and Laboratory Medicine, Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, 212013, China.China
- 通讯作者单位
- Jiangsu Province Key Laboratory of Medical Science and Laboratory Medicine, Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, 212013, China. lstmmmlst@163.com.China
- 期刊
- Journal of nanobiotechnology2024 Jul 29
- 原文标识
- PubMed 39075563 · DOI 10.1186/s12951-024-02676-1
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 →