前进一步:防止瘤适应免疫疗法
Erica L Braverman1,2, Giuliana P Mognol3, Andy J Minn4,5
1Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA.
概括
免疫检查点抑制剂提供癌症治疗的好处,但面临抵抗和副作用. 针对LAG-3和干扰素信号传导等替代检查点的新疗法显示,改善抗瘤免疫力是有前途的.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 癌症治疗方法 癌症治疗方法
背景情况:
- 免疫检查点抑制剂 (ICI) 已经彻底改变了癌症治疗,改善了几种癌症类型的生存率.
- 然而,许多患者对ICI没有反应,获得的耐药性或严重的不良事件限制了其有效性.
- 抵抗的机制包括T细胞耗尽,替代检查点的上调 (例如LAG-3),持续的干扰素信号和瘤微环境 (TME) 中的免疫抑制髓状细胞.
研究的目的:
- 审查固体瘤中对免疫检查点抑制剂的抵抗机制.
- 突出针对替代免疫检查点和参与免疫抑制的途径的新兴治疗策略.
- 讨论癌症新型免疫疗法的最新临床发展和批准.
主要方法:
- 对免疫检查点抑制剂和癌症抵抗机制研究的文献综述.
- 对针对替代检查点和免疫抑制途径的新型免疫疗法的临床试验数据的分析.
- 检查T细胞耗尽,LAG-3,干扰素信号传递和TME中的髓状细胞的作用.
主要成果:
- 慢性免疫刺激可以导致T细胞疲劳和LAG-3等替代检查点的升调.
- 在TME中持续的干扰素信号传递可以诱导癌细胞的表观遗传变化,促进免疫逃避.
- 免疫抑制性巨细胞通过阻碍有效的抗瘤免疫反应,促进瘤的进展.
- 针对LAG-3,氏酸3-激酶玛和JAK抑制剂的新疗法显示出临床前景.
结论:
- 了解抵抗机制对于推进癌症免疫治疗至关重要.
- 针对其他免疫检查点和免疫抑制途径为癌症治疗提供了新的途径.
- 新兴疗法显示出克服耐药性和改善更广泛癌症患者治疗结果的潜力.
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