向瘤相关巨细胞的MS4A4A恢复了CD8+T细胞介导的抗瘤免疫力
Yongsheng Li1,2, Zhiyong Shen1,2, Zhen Chai1,2
1Department of General Surgery, Southern Medical University Nanfang Hospital, Guangzhou, Guangdong, China.
Gut
|July 28, 2023
概括
针对瘤相关的巨细胞的MS4A4A增强了癌症免疫疗法. 阻断MS4A4A通过增加效应T细胞和减少免疫抑制细胞来提高免疫检查点抑制剂的疗效,提供了一种新的抗癌策略.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- 免疫检查点抑制剂 (ICI) 释放T细胞对瘤的活性,但受到免疫抑制性髓状细胞的阻碍.
- 跨膜蛋白MS4A4A在与瘤相关的巨细胞 (TAMs) 中高度表达,这是瘤免疫微环境的关键调节者.
研究的目的:
- 为了研究MS4A4A+TAMs在瘤免疫逃生中的作用.
- 开发针对TAM的治疗策略,以提高ICI在结直肠癌中的疗效.
主要方法:
- 用小鼠瘤模型 (皮下和正管) 来评估单独和ICI的MS4A4A阻塞效应.
- 通过流细胞计和质细胞计分析瘤免疫微环境的变化.
- 通过使用RNA测序和西部斑点来探索MS4A4A介导的M2巨细胞极化分子机制.
主要成果:
- 在TAM中MS4A4A的表达与癌症患者的不良临床结果相关.
- 阻断MS4A4A,包括抗MS4A4A抗体,减少瘤生长和改善ICI治疗的有效性.
- MS4A4A阻塞调节了瘤免疫微环境,减少了M2-TAM和耗尽的T细胞,同时增加了 CD8+ T细胞.
- 联合抗MS4A4A和抗PD-1疗法在治疗耐药瘤中显示出有效性,并且在放射治疗中诱导完全回归.
- MS4A4A通过PI3K/AKT和JAK/STAT6信号通路促进M2巨细胞的极化.
结论:
- 针对MS4A4A是一个有希望的战略,以提高ICI的有效性.
- MS4A4A封锁为抗癌免疫疗法提供了一种新的治疗方法.
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