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
用 Gpc3 适配体修饰的 NK 细胞增强肝细胞癌的过继免疫治疗
英文原题：Natural killer cells modified with a Gpc3 aptamer enhance adoptive immunotherapy for hepatocellular carcinoma.
查看英文原题
Natural killer cells modified with a Gpc3 aptamer enhance adoptive immunotherapy for hepatocellular carcinoma.
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研究概要
所提出的策略赋予 NK 细胞肿瘤特异性靶向能力，从而增强其在 GPC3+肝细胞癌中的过继治疗效率。
研究思路结论见上方概要
背景
NK 细胞无需预先致敏即可攻击癌细胞，但其临床获益有限，原因在于其缺乏靶向肿瘤细胞的特异性受体，导致选择性较差。在本研究中，我们旨在赋予NK细胞特异性靶向glypican-3+肿瘤细胞的能力，且不产生细胞损伤或基因改变，并进一步评估其治疗效率。
方法
NK细胞通过代谢糖工程在细胞表面修饰Gpc3 DNA适配体，从而赋予NK细胞特异性靶向能力。随后，在体外评估了G-NK细胞的特异性靶向特性、细胞毒性和细胞因子分泌。最后，我们在体内研究了G-NK细胞对glypican-3+肿瘤细胞的治疗效果。
结果
与随机适配体突变修饰的NK细胞和未修饰的NK细胞相比，G-NK细胞诱导GPC3+肿瘤细胞发生显著的凋亡/坏死，并分泌细胞因子以维持强烈的细胞毒性活性。此外，由于G-NK细胞在肿瘤部位的富集增强，G-NK细胞显著抑制了HepG2荷瘤小鼠的肿瘤生长。
展开英文摘要原文
METHODS
NK cells were modified with a Gpc3 DNA aptamer on the cell surface via metabolic glycoengineering to endow NK cells with specific targeting ability. Then, the G-NK cells were evaluated for their specific targeting properties, cytotoxicity and secretion of cytokines in vitro. Finally, we investigated the therapeutic efficiency of G-NK cells against glypican-3 + tumor cells in vivo.
RESULTS
Compared with NK cells modified with a random aptamer mutation and unmodified NK cells, G-NK cells induced significant apoptosis/necrosis of GPC3 + tumor cells and secreted cytokines to preserve the intense cytotoxic activities. Moreover, G-NK cells significantly suppressed tumor growth in HepG2 tumor-bearing mice due to the enhanced enrichment of G-NK cells at the tumor site.
CONCLUSIONS
The proposed strategy endows NK cells with a tumor-specific targeting ability to enhance adoptive therapeutic efficiency in GPC3 + hepatocellular carcinoma.
论文信息
- 作者
- Zheng Y、Lai Z、Wang B、Wei Z、Zeng Y、Zhuang Q、Liu X、Lin K
- 第一作者单位
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, People's Republic of China.China
- 通讯作者单位
- Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, China. kclin2002@126.com.China
- 期刊
- Discover oncology2023 Sep 4
- 原文标识
- PubMed 37665421 · DOI 10.1007/s12672-023-00780-6
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