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
用于肿瘤过继细胞治疗筛选的记忆样 NK 细胞的表型与分子变异性分析
英文原题：Analysis of Phenotypic and Molecular Variability of Memory-like NK Cells for Cancer Adoptive Cell Therapy Screening.
查看英文原题
Analysis of Phenotypic and Molecular Variability of Memory-like NK Cells for Cancer Adoptive Cell Therapy Screening.
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研究概要
我们的研究结果为区分 mlNK 细胞产品提供了见解，并揭示了预测性标志物如何能够识别出用于癌症过继细胞治疗的最佳 mlNK 细胞产品。
研究思路结论见上方概要
背景
过继性细胞疗法正逐渐成为治疗血液系统恶性肿瘤和实体瘤的一种有前景的治疗选择。记忆样自然杀伤（mlNK）细胞是经细胞因子预激活后产生的一种特定NK细胞亚型，已在输注患者后显示出增强的体内持久性，而这一问题一直阻碍着传统NK细胞免疫疗法的发展。然而，mlNK细胞产品的质量及变异性仍缺乏明确界定。
方法
在本研究中，我们评估了来自不同供体的mlNK细胞在关键功能和分子方面的异质性，包括mlNK细胞毒性、簇形成、运动性、线粒体形态和基因表达。
结果
我们观察到与糖酵解相关的基因表达变化和NK细胞关键功能（如细胞毒性和运动性）之间存在相关性。为进一步表征，我们阻断了糖酵解和氧化磷酸化（OXPHOS），并观察到mlNK功能反应受损，提示代谢的重要性。
展开英文摘要原文
BACKGROUND
Adoptive cell therapies are emerging as a promising therapeutic option against hematological and solid malignancies. Memory-like natural killer (mlNK) cells are a specific subtype of NK cells generated after cytokine preactivation that have shown enhanced in vivo persistence after infusion into patients, an issue that has hindered traditional NK cell immunotherapy. However, the quality and variability of mlNK cell products remains poorly defined.
METHODS
In this study, we evaluated heterogeneity across critical functional and molecular aspects of mlNK cells generated from independent donors, including mlNK cytotoxicity, cluster formation, motility, mitochondria morphology, and gene expression.
RESULTS
We observed a correlation between changes in gene expression associated with glycolysis and key NK cell functions such as cytotoxicity and motility. For further characterization, we blocked glycolysis and oxidative phosphorylation (OXPHOS) and observed an impaired mlNK functional response, suggesting the importance of metabolism.
CONCLUSIONS
Our findings provide insights into discriminating between mlNK cell products and how the predictive markers can identify optimal mlNK cell products for adoptive cell therapy of cancer.
论文信息
- 作者
- Turaga RV、Zima SRT、Peterson EP、Erbe AK、Forsberg MH、Capitini CM、Cosper PF、Sondel PM
- 单位
- Department of Dermatology, School of Medicine and Public Health, University of Wisconsin, 1 S Park Street, Madison, WI 53715, USA.United States
- 期刊
- Cancers2025 Jul 9
- 原文标识
- PubMed 40723171 · DOI 10.3390/cancers17142288
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