文章：

记忆样自然杀伤细胞在癌症过继细胞疗法筛选中的表型与分子变异性分析

Analysis of Phenotypic and Molecular Variability of Memory-like NK Cells for Cancer Adoptive Cell Therapy Screening

原文发布日期：9 July 2025

DOI: 10.3390/cancers17142288

类型: Article

开放获取: 是

英文摘要：

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.

摘要翻译： 

背景：过继性细胞疗法正成为对抗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）细胞是细胞因子预激活后产生的一种特定NK细胞亚型，在输注患者体内后显示出增强的体内持久性，而持久性不足正是传统NK细胞免疫疗法面临的主要障碍。然而，mlNK细胞产品的质量与异质性仍未得到充分界定。 方法：本研究评估了来自不同供体的mlNK细胞在关键功能与分子层面的异质性，包括mlNK细胞的细胞毒性、簇形成能力、运动性、线粒体形态及基因表达。 结果：我们观察到与糖酵解相关的基因表达变化与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，我们阻断糖酵解和氧化磷酸化（OXPHOS）后，发现mlNK细胞功能反应受损，提示代谢调控的重要性。 结论：本研究为区分mlNK细胞产品提供了新见解，并揭示了如何利用预测性标志物筛选适用于癌症过继性细胞治疗的最佳mlNK细胞产品。

原文链接：

Analysis of Phenotypic and Molecular Variability of Memory-like NK Cells for Cancer Adoptive Cell Therapy Screening