向乳化增强了瘤微环境中的NK细胞细胞毒性
Jing Jin1, Peidong Yan1, Dongyao Wang2
1National Key Laboratory of Immune Response and Immunotherapy; Department of Hepatobiliary Surgery, The First Affiliated Hospital of USTC, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
瘤衍生乳酸通过氨酸乳化 (Kla) 损害了自然杀手 (NK) 细胞. 补充尼古丁胺胺氨基二核酸 (NAD+) 前体和SIRT3激活剂可以增强NK细胞对白血病的细胞毒性.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 生物化学 生化学
背景情况:
- 瘤微环境中的自然杀手 (NK) 细胞功能障碍与乳酸有关.
- 氨酸乳酸化 (Kla),是一种乳酸诱导的翻译后修饰,可以损害NK细胞的功能.
- 向Kla可能会增强NK细胞介导的癌症免疫疗法.
研究的目的:
- 研究Kla对NK细胞代谢和细胞毒性的影响.
- 确定增强NK细胞对乳酸诱导的Kla.抗性的策略.
- 评估针对白血病的联合干预措施的治疗潜力.
主要方法:
- 评估了Kla水平,尼古丁胺氨酸二核酸 (NAD+) 代谢,线粒体完整性和NK细胞中的细胞毒性.
- 给NK细胞注射尼古丁胺 рибоoside (NAD+前体) 和 honokiol (SIRT3激活剂).
- 评估了这些干预措施对NK细胞抗白血病活性的作用,ex vivo和in vivo.
主要成果:
- 增加的Kla水平与NAD+代谢受损,线粒体分裂和NK细胞细胞毒性降低相关.
- 联合补充尼古丁胺胺 рибоoside 和 honokiol 降低了细胞 Kla 水平,并增强了 NK 细胞细胞毒性.
- 这种组合疗法通过抑制ROCK1-DRP1信号传递和防止线粒体分裂,恢复了NK细胞的抗白血病活性.
结论:
- 乳化通过影响NAD+代谢和线粒体完整性,损害NK细胞功能.
- 向Kla代表了增强NK细胞基础免疫疗法的有希望的策略.
- 综合干预可以改善NK细胞对富含乳酸的瘤微环境的抵抗力.
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