癌细胞中的Acod1表达通过生成抑制性的过程促进了免疫逃避
James H Schofield1, Joseph Longo2, Ryan D Sheldon3
1Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556, USA.
Cell reports
|March 23, 2024
概括
抵抗PD-1疗法的癌细胞通过Acod1产生伊塔康酸,抑制T细胞生长. 减少Acod1通过阻断抑制性质使瘤对PD-1疗法的敏感.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 代谢过程中的代谢.
背景情况:
- 免疫检查点阻塞 (ICB) 针对编程细胞死亡蛋白1 (PD-1) 是一种关键的癌症治疗方法.
- 由代谢物驱动的瘤微环境免疫抑制,限制了许多癌症中的ICB疗效.
研究的目的:
- 研究 itaconate (ITA) 和aconite脱碳酶 (Acod1) 在抵抗 PD-1 阻塞中的作用.
- 阐明Acod1在瘤微环境中促进免疫抑制的机制.
主要方法:
- 在αPD-1-抗性癌细胞中分析Acod1和ITA水平.
- 在癌细胞中对Acod1表达的基因操纵.
- 在共同培养系统中评估CD8+T细胞的增殖和功能.
主要成果:
- 抗阿尔法PD-1的癌细胞表现出Acod1的增加,导致ITA的高产量.
- 降低抗性细胞中的Acod1水平恢复了对alphaPD-1疗法的敏感性.
- 具有高Acod1的癌细胞通过分泌的抑制性,而不是ITA,抑制了天真的CD8+T细胞增殖.
结论:
- 在癌症中,Acod1是抵抗PD-1阻塞的关键媒介.
- 向Acod1活动可以克服免疫抑制并使瘤对ICB治疗敏感.
- 抑制性,而不是ITA,调解了Acod1依赖的CD8+T细胞抑制.
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