对T细胞参与者的抵抗机制的机理洞察力
Linlin Cao1, Gabrielle Leclercq-Cohen1, Christian Klein2
1Roche Innovation Center, Zürich, Switzerland.
Frontiers in immunology
|May 7, 2025
概括
通过引导T细胞杀死瘤细胞,T细胞参与剂 (TCE) 显示出治疗癌症的前景. 本综述详细介绍了抗药性机制和改善TCE治疗有效性的策略.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
背景情况:
- T细胞参与剂 (TCEs) 通过重定向T细胞以消除癌细胞,有效治疗B细胞恶性瘤和固体瘤.
- 尽管临床成功,但患者对TCE治疗的耐药性,无论是原发性还是获得性,都限制了治疗的有效性.
- 了解耐药机制对于优化基于TCE的癌症治疗至关重要.
研究的目的:
- 在临床前模型和临床试验中全面审查对TCE的耐药性机制.
- 将抗性分为瘤内在和瘤外在的类别.
- 提出克服TCE耐药性和提高临床疗效的策略.
主要方法:
- 对TCE耐药性的临床前模型和临床试验的文献综述.
- 将抗性机制分为瘤内在因素和瘤外在因素.
- 基于TCE耐药性的细胞和分子通路的分析.
主要成果:
- 瘤内在的抵抗机制包括抗原损失和免疫检查点连接体的表达.
- 瘤外部抵抗机制涉及免疫抑制瘤微环境和T细胞功能受损.
- 这两种机制都有助于减少T细胞介导的对癌细胞的细胞毒性.
结论:
- 对TCE的抵抗是多因素的,涉及瘤细胞自主和微环境依赖的因素.
- 识别和准这些抵抗机制可以改善患者的治疗结果.
- 开发克服抗性的策略是释放TCE在癌症治疗中的全部潜力的关键.
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