扩展的适应性NKG2C+NK细胞表现出强大的ADCC和对HBV感染的肝瘤细胞系的功能反应
bioRxiv : the preprint server for biology
|June 12, 2025
概括
自适应性自然杀手 (NK) 细胞从慢性乙型肝炎病毒 (HBV) 感染的患者中成功扩展. 这些增强的NK细胞显示出治疗HBV相关肝病和癌症的前景.
科学领域:
- 免疫学 免疫学 免疫学
- 肝病学 肝病学是一种肝病学.
- 癌症研究 癌症研究
背景情况:
- 乙型肝炎病毒 (HBV) 感染导致慢性肝病和肝细胞癌 (HCC).
- 自然杀手 (NK) 细胞与HBV感染的细胞作斗争,但在慢性感染中,它们的功能下降.
- 被NKG2C标记的自适应性NK细胞提供了改善抗HBV免疫力和癌症治疗的潜力.
研究的目的:
- 扩展和特征自适应性NK细胞从慢性HBV感染的个体,与或没有艾滋病毒的同时感染.
- 评估扩展适应性NK细胞对抗肝瘤细胞系的功能能力.
- 调查TGF-β预先调节用于肝脏向免疫治疗的潜力.
主要方法:
- 从冷保存的PBMC中使用K562-HLA-E料细胞和IL-2扩展适应性NK细胞.
- 对NK细胞表型 (NKG2C,CD16,Granzyme B),细胞毒性和ADCC的评估.
- 对各种肝瘤细胞系和自身T细胞的功能反应的评估.
- 在TGF-β预先条件下诱导组织内定标记物 (CD103,CD49a).
主要成果:
- 达到>97%的纯度和适应性NK细胞的100倍扩张,具有高NKG2C和Granzyme B表达.
- 扩张的NK细胞表现出增强的ADCC和对肝瘤细胞的功能反应.
- 在TGF-β预条件诱导的组织居民标记物中,同时保持NK细胞的功能.
- 对自身T细胞的最小反应性表明了有利的安全性.
结论:
- 从患有慢性病毒感染的捐赠者获得的功能性适应性NK细胞的首次成功扩张.
- 这种方法为基于NK细胞的治疗提供了基础,用于HBV功能治愈和HCC治疗.
- 与单克隆抗体的组合疗法可能进一步增强HBV治疗策略.
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