瘤细胞表达的脂解刺激的脂蛋白受体负面调节T细胞功能
Masashi Funauchi1,2,3, Satoshi Serada2, Kosuke Hiramatsu1
1Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka, Japan.
International journal of cancer
|September 20, 2023
概括
脂解刺激的脂蛋白受体 (LSR) 起到免疫检查点的作用,抑制瘤中的CD8+T细胞活性. 用一种新型抗体向LSR显示出显著的抗瘤效应,为癌症免疫治疗提供了一条新的途径.
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:
- 脂解刺激的脂蛋白受体 (LSR) 在各种固体瘤中表达,并且与预后不佳有关.
- 它在癌症中,特别是免疫调节中的确切作用仍然不清楚.
- LSR属于Ig蛋白超级家族,与B7家族共享保存域.
研究的目的:
- 为了研究脂解刺激脂蛋白受体 (LSR) 作为一种新的免疫检查点分子.
- 在癌症模型中评估准LSR的治疗潜力.
主要方法:
- 开发一种新的抗LSR抗体 (#27-6 mF-18),对人类和小鼠的LSR具有交叉反应性.
- 在4T1小鼠乳腺癌模型中评估抗体的疗效.
- 分析瘤透免疫细胞,特别是CD8+ T细胞,以及CD8+ T细胞枯竭的影响.
主要成果:
- 在4T1模型中,抗LSR抗体 (#27-6mF-18) 显示出显著的抗瘤效应,即使在免疫性较差的环境中.
- 用抗LSR抗体治疗导致瘤微环境中CD8+T细胞的透和激活增加.
- 观察到的抗瘤效应取决于CD8+ T细胞,因为耗尽取消了治疗效益.
结论:
- 脂解刺激的脂蛋白受体 (LSR) 通过抑制CD8+T细胞活性,起到抗瘤免疫的负调节作用.
- 准LSR代表了开发新型癌症免疫疗法和免疫检查点抑制剂的有希望的战略.
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