脂质积累介导的组织素低乙化驱动了抗瘤免疫中的持续性NK细胞功能障碍
Deyan Jiao1, Renhui Sun1, Xiaolei Ren1
1Key Laboratory for Experimental Teratology of Ministry of Education, Key Laboratory of Infection and Immunity of Shandong Province and Department of Immunology, School of Basic Medical Sciences, Cheeloo Medical College of Shandong University, Jinan, Shandong, China.
Cell reports
|October 4, 2023
概括
高脂肪饮食通过改变c-Myc乙化,损害抗瘤免疫力,导致持久的自然杀手 (NK) 细胞功能障碍. 经过改造的c-Myc的工程NK细胞显示在高脂血症中改善了对抗瘤的能力.
科学领域:
- 免疫学 免疫学 免疫学
- 代谢综合征是代谢综合征的一种.
- 癌症生物学 癌症生物学
背景情况:
- 超脂血症与癌症发病率和死亡率的增加有关.
- 超脂血症损害抗瘤免疫力的机制尚未完全理解.
研究的目的:
- 在高脂血症条件下研究自然杀手 (NK) 细胞的持续功能缺陷.
- 阐明在高脂血症中NK细胞功能障碍背后的分子机制.
- 探索工程NK细胞用于癌症免疫治疗的潜力.
主要方法:
- 从高脂肪饮食的小鼠中分离出NK细胞,或在体外用油酸 (OA) 处理.
- 分析了染色质可访问性,c-Myc乙化,蛋白质半衰期和H3K27乙化.
- NK细胞是用高乙化c-Myc突变体进行的.
主要成果:
- 超脂血症诱导可持续的NK细胞功能缺陷,即使在从脂质丰富的环境中移除后.
- 对OA的暴露降低了NK细胞效应分子促进者的染色质可访问性.
- 甲损害了P300介导的c-Myc乙化,缩短了它的半衰期,导致持续的NK细胞功能障碍.
结论:
- 超脂血症通过涉及c-Myc乙化的表观遗传修饰导致持续的NK细胞功能障碍.
- 具有高乙化c-Myc突变体的工程NK细胞可以克服高脂血症诱导的抑制.
- 工程NK细胞代表了增强抗瘤免疫疗法的有希望的策略,在失脂症的背景下.
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