黑色素瘤对免疫治疗的反应蛋白学揭示了线粒体依赖性
Michal Harel1, Rona Ortenberg2, Siva Karthik Varanasi3
1Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 6997801, Israel.
Cell
|September 10, 2019
概括
响应免疫治疗的黑色素瘤患者的氧化和脂质代谢水平较高. 提高脂质代谢可以改善癌症免疫性和患者对免疫治疗的反应.
科学领域:
- 癌症学
- 免疫学
- 代谢学
背景情况:
- 免疫疗法改变了癌症治疗,
- 了解反应机制对于改善患者的结果至关重要.
研究的目的:
- 调查与黑色素瘤免疫治疗反应相关的蛋白质特征.
- 阐明细胞代谢在黑色素瘤免疫性和免疫治疗反应中的作用.
主要方法:
- 使用高分辨率质谱测试对接受免疫治疗的黑色素瘤患者的临床样本进行蛋白质分析.
- 分析了超过10300个样本中的蛋白质.
- 在体外和体内实验涉及代谢干扰和CRISPR-Cas9敲除黑色素瘤细胞.
主要成果:
- 与没有反应者相比,对基于瘤透淋巴细胞 (TIL) 和抗编程死亡1 (PD1) 免疫疗法的反应者呈现出更高的氧化酸化和脂质代谢.
- 脂质代谢被确定为黑色素瘤免疫性的关键调节者.
- 增加脂质代谢增强了抗原呈现,导致对T细胞间接杀死的敏感性更大.
结论:
- 黑色素瘤的代谢状态,特别是脂质代谢,与免疫治疗反应有很强的关联.
- 向脂质代谢途径是增强黑色素瘤免疫性和提高治疗功效的潜在策略.
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