克服对癌症免疫检查点治疗的获得性耐药性:基于分子机制的潜在策略
Bin Wang1,2, Yin Han3, Yuyu Zhang1,4,5
1Department of Radiation Oncology, The First Hospital of Jilin University, 71 Xinmin Street, Changchun, 130021, China.
Cell & bioscience
|June 29, 2023
概括
对免疫检查点抑制剂 (ICI) 的获得性耐药性是癌症治疗的一个主要挑战. 本综述探讨了抗原呈现问题和微生物组变化等机制,并讨论了克服ICI耐药性的策略,以获得更好的患者结果.
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:
- 针对CTLA-4和PD-1/PD-L1的免疫检查点抑制剂 (ICI) 已经推进了癌症治疗,为各种恶性瘤提供了持久的反应和更好的生存率.
- 在初始反应后对ICI获得的耐药性是一个重要的障碍,限制了长期的疗效.
- 了解获得性耐药性的机制对于开发有效的治疗策略至关重要.
研究的目的:
- 审查目前对免疫检查点抑制剂 (ICI) 获得耐药性的机制的理解.
- 讨论潜在的治疗策略,旨在逆转ICI耐药性,并改善癌症患者的临床益处.
主要方法:
- 文献综述侧重于对ICI获得的抗药性机制.
- 分析导致耐药性的因素,包括抗原呈现,信号通路,免疫微环境,表观遗传修饰和肠道微生物组失调.
- 探索克服ICI耐药性的治疗策略.
主要成果:
- 获得性耐药性的关键机制包括缺乏新抗原,抗原呈现受损,IFN-γ/JAK信号的突变,替代性免疫检查点的激活,免疫抑制性瘤微环境,表观遗传改变和肠道微生物组失调.
- 这些机制共同导致抗瘤T细胞免疫力丧失.
- 基于这些已识别的机制,讨论了扭转电阻的潜在策略.
结论:
- 对ICI获得的耐药性是多因素的,涉及瘤及其微观环境中的复杂相互作用.
- 针对这些抗药性机制为提高ICI有效性提供了有希望的途径.
- 对克服ICI耐药性的进一步研究对于改善癌症患者的治疗结果至关重要.
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