加尔-3 阻断了PD-1 和 pembrolizumab 之间的结合
Stinne Ravn Greisen1,2, Mia Bendix3, Morten Aagaard Nielsen4,2
1Rheumatology, Aarhus University Hospital, Aarhus, Denmark srg@biomed.au.dk.
Journal for immunotherapy of cancer
|October 2, 2024
概括
加勒-3 阻断了布罗利祖马布与PD-1 的结合,阻碍了转移性黑色素瘤的免疫反应. 瘤中高高的加勒-3与瘤的进展相关,而高血水平表明更长的生存期,这表明治疗反应中具有复杂的作用.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 生物化学 生化学
背景情况:
- 免疫检查点抑制剂 (ICI) 改善了转移性恶性黑色素瘤 (MM) 的存活率.
- 预测ICI反应的生物标记因某些患者的治疗耐药性至关重要.
- 加勒-3 (Gal-3) 是ICI治疗的潜在生物标志物和治疗标.
研究的目的:
- 在转移性MM中研究编程细胞死亡1 (PD-1),布罗利祖马布和Gal-3之间的相互作用.
- 确定Gal-3是否影响pembrolizumab的疗效.
- 探索Gal-3作为ICI治疗反应的预测生物标志物.
主要方法:
- 表面等离子体共振 (SPR) 和低温电子显微镜 (cryo-EM) 用于可视化结合相互作用.
- 在体外T细胞培养物中评估细胞因子的产生.
- 用pembrolizumab治疗的转移性MM患者的可溶性PD-1和Gal-3水平的测量.
主要成果:
- 证明Gal-3可以通过固体抑制来阻止PD-1和pembrolizumab的结合.
- -3降低了T细胞促炎性细胞因子的产生,不受 pembrolizumab 的影响.
- 高瘤Gal-3与疾病进展相关,而高血Gal-3与更长的无进展生存相关.
- 可溶性PD-1水平在佩姆布里祖马布治疗后增加,与疾病进展相关.
结论:
- PD-1和Gal-3之间的相互作用干扰着pembrolizumab的结合.
- 瘤微环境中的Gal-3诱导的免疫抑制不能被 pembrolizumab 克服.
- 在ICI治疗结果方面,Gal-3在血和瘤组织中表现出不同的作用.
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