在单细胞上准CD93通过增强CD8+ T细胞的功能和透来振兴抗瘤免疫力
Da Jiang1,2, Aiqi Huang1, Bai-Xi Zhu1
1Sun Yat-sen University School of Life Science, Guangzhou, Guangdong, China.
Journal for immunotherapy of cancer
|October 24, 2024
概括
肝细胞癌 (HCC) 中的CD93+单细胞限制了CD8+ T细胞的透. 向CD93增强T细胞活性,并在临床前模型中改善免疫治疗反应.
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:
- 有限的CD8+T细胞激活和透阻碍了基于T细胞的免疫治疗固体瘤.
- 这些限制背后的确切机制仍然不完全理解.
研究的目的:
- 调查CD93表达在肝细胞癌 (HCC) 中单细胞上的作用.
- 阐明CD93+单细胞影响CD8+T细胞功能和瘤排除的机制.
- 评估CD93作为HCC的潜在免疫治疗点.
主要方法:
- 评估了人类HCC组织 (非瘤,周瘤,瘤) 中单细胞上的CD93表达.
- 进行了体外和体内实验,以研究CD93+单细胞对CD8+T细胞的影响.
- 研究了涉及的信号通路 (Erk,AKT-GSK3β) 和分子相互作用 (versican,hyaluronan,原体).
主要成果:
- 在周围瘤HCC组织中的单细胞上,CD93表达显著升高.
- CD93+单细胞与瘤内的CD8+T细胞密度降低有关.
- CD93上调PD-L1并诱导单细胞的维西卡生产,抑制CD8+ T细胞迁移.
- 在体内向CD93增加了CD8+T细胞的透和激活,提高了抗PD-1疗法的疗效.
结论:
- 确定了一种涉及CD93+单细胞的新机制,该机制有助于HCK中CD8+T细胞功能受损.
- CD93+单细胞是HCC治疗中一个有前途的免疫治疗点.
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