lysosome 阻塞诱导巨细胞和瘤中不同的代谢程序,用于癌症免疫治疗
Jing Ma1, Ruijuan Ma1, Xueke Zeng2
1School of Pharmacy, Institute of Chemical Biology, Henan Province Engineering Research Center of High Value Utilization to Natural Medical Resource in Yellow River Basin, State key Laboratory of Antiviral Drugs, School of Pharmacy, Henan University, Kaifeng, 475004, Henan, China.
Journal of experimental & clinical cancer research : CR
|August 3, 2023
概括
这项研究引入了纳夫,一种新型的金属药物,可以重新编程与瘤相关的巨细胞,并准溶酶体代谢,以增强癌症免疫疗法. 它提供了一种超越DNA抑制的新策略,用于治疗各种癌症类型.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 药物发现 药物发现 药物发现
背景情况:
- 基于的化疗可以促进M2巨细胞,导致免疫抑制和较差的抗转移活性.
- Lysosome代谢在癌症入侵和抗瘤免疫中的作用尚未完全理解.
- 目前的策略旨在克服免疫抑制瘤微环境.
研究的目的:
- 探索一种协同策略来拆除免疫抑制瘤微环境.
- 为了发现利用代谢可塑性用于癌症治疗的金属药物.
- 研究纳夫在重编程巨细胞和瘤细胞中的机制.
主要方法:
- 纳夫普拉丁合成以调节 lysosomal 功能.
- 在体内测试使用结直肠癌细胞和血液,瘤和脏组织的分析.
- 流细胞计,RNA测序 (RNA-seq) 和对MCOLN1,MAPK,HMGB1和CTSL的机械学研究.
主要成果:
- 纳夫重新编程巨细胞,终止TAMs-MDSCs-Treg免疫抑制轴.
- 纳夫拉丁通过MCOLN1诱导巨细胞中的溶酶体代谢激活,导致M1极化.
- 在癌细胞中,HMGB1介导的溶酶体阻断促进了抗瘤效应.
结论:
- 纳夫提供基于巨细胞的金属药物策略,用于治疗"热"和"冷"癌症.
- 这种方法针对癌症免疫治疗的溶酶体代谢,与传统的DNA抑制金药物不同.
- 这项研究揭示了癌症免疫治疗中金属药物发现的关键策略.
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