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梅瓦酸盐通过稳定CD274mRNA来提高抗PD-1/PD-L1的疗效

Wenxin Zhang¹, Xiaohui Pan¹, Yanjun Xu²

¹Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.

Acta pharmaceutica Sinica. B

|July 10, 2023

概括

较高的血甲酸盐水平与非小细胞肺癌中对抗编程死亡-结体治疗的更好反应相关. 梅瓦诺酸补充剂增强了抗瘤免疫力和PD-L1表达,表明其作为免疫敏感剂的潜力.

科学领域:

免疫学免疫学免疫学
代谢途径代谢途径
在瘤学瘤学.

背景情况:

梅瓦诺酸代谢对瘤进展至关重要,但其在免疫逃避和检查点调节中的作用尚不清楚.
非小细胞肺癌 (NSCLC) 治疗疗效可能受到免疫逃避机制的限制.

研究的目的:

调查美瓦酸盐代谢在NSCLC免疫检查点调节中的作用.
为了确定血中甲基酸盐水平与对抗编程死亡-联结体1 (PD-L) 1) 治疗的反应之间的相关性.

主要方法:

对血甲酸盐水平的分析以及与NSCLC患者无进展生存率和整体生存率的相关性.
使用NSCLC细胞系进行体外研究,以评估mevalonate对编程死亡配体1 (PD-L1) 表达的作用.
调查基于氨酸诱导的PD-L1调节的分子机制,包括mRNA稳定性和蛋白质结合.
在体内研究,以评估梅瓦酸盐补充剂对抗PD-(L) 1治疗疗效和T细胞反应的影响.

主要成果:

较高的血甲酸盐水平与接受抗PD-L治疗的NSCLC患者的改善结局有关.
梅瓦诺酸补充剂通过通过HuR结合来增强CD274mRNA稳定性,从而提高NSCLC细胞中PD-L1表达的调节.
梅瓦酸盐的添加改善了体内抗PD-(L) 1的抗瘤作用,增加了CD8+T细胞透和细胞毒性功能.

结论:

血甲酸盐水平是预测NSCLC中抗PD-(L) 1治疗反应的潜在生物标志物.
梅瓦诺酸补充剂可以作为免疫敏感剂,增强NSCLC免疫检查点阻塞治疗的疗效.

关键词:

这就是 HuRR 的意思.免疫检查站封锁免疫检查站封锁它的代谢物是代谢物.梅瓦诺酸是什么意思梅瓦诺酸是什么意思在NSCLCLC中,我们可以看到.在PD-L1中.在mRNA的稳定性上.

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