阻断免疫检查点LAG-3和PD-1对人类不变的自然杀手T细胞功能的影响
Allison L Balasko1, Monika M Kowatsch1, Colin Graydon1
1Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Canada.
Scientific reports
|June 21, 2023
概括
阻断免疫检查点蛋白编程细胞死亡-1 (PD-1) 和淋巴细胞激活基因-3 (LAG-3) 可以增强不变的自然杀手T (iNKT) 细胞功能. 对PD-1和LAG-3的双重阻断显示出对抗免疫衰竭的前景.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 癌症研究 癌症研究
背景情况:
- 不变的自然杀手T (iNKT) 细胞对于免疫反应至关重要,但在癌症和艾滋病毒等慢性疾病期间可能会耗尽.
- 在iNKT细胞中,免疫衰竭的特征是免疫检查点蛋白的功能障碍和增加表达,包括PD-1和LAG-3.
研究的目的:
- 研究阻断PD-1和LAG-3以恢复iNKT细胞功能的潜力.
- 评估抗PD-1和抗LAG-3抗体疗法在增强iNKT细胞增殖和干扰素- (IFN-γ) 生产方面的疗效.
主要方法:
- 来自健康捐赠者的外周血液单核细胞用α-galactosylceramide进行了刺激.
- 流细胞计用于测量iNKT细胞上的LAG-3和PD-1表达.
- 一项为期10天的阻断试验评估了抗PD-1和抗LAG-3抗体对iNKT细胞增殖和IFN-γ产生的影响.
主要成果:
- 在iNKT细胞上的LAG-3和PD-1表达在刺激后的第四天达到峰值.
- 与对照组相比,抗PD-1和双抗PD-1/抗LAG-3阻塞都显著增加了iNKT细胞的增殖.
- 双阻塞策略在增强iNKT细胞增殖方面表现出卓越的有效性.
结论:
- PD-1和LAG-3作为可行的免疫治疗点,用于增强人类iNKT细胞功能.
- 针对这些免疫检查点提供了一种潜在的策略,以克服iNKT细胞中的免疫疲劳.
- 双重阻断PD-1和LAG-3为改善iNKT细胞介导免疫提供了一个有希望的方法.
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