在结肠直肠癌中解码免疫疗法反应:超越MSI的翻译见解
Chiara Cataldi1, Beliz Bahar Karaoğlan2, Elena Liotta3
1Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy.
Cancers
|March 14, 2026
概括
免疫检查点抑制剂 (ICI) 在结直肠癌 (CRC) 中表现有前途,但耐药性很常见. 除了不匹配修复缺陷之外,还需要新的生物标志物来预测反应,并指导组合疗法,以便更好地选择患者.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 遗传学 是一个遗传学.
背景情况:
- 免疫检查点抑制剂 (ICI) 为各种癌症,包括结肠直肠癌 (CRC) 提供了转变性治疗.
- 目前ICI在CRC中的有效性主要局限于不匹配的维修缺陷 (dMMR) 或微卫星不稳定性高 (MSI-H) 亚型.
- 对ICI的原发性和获得性耐药性限制了临床益处,需要进一步发现生物标志物.
研究的目的:
- 审查预测结直肠癌中ICI反应和耐药性的既定和新兴生物标志物.
- 综合临床试验,转化研究和关于CRC免疫疗法生物标志物的评论的证据.
- 为患者选择提供信息,并开发用于CRC治疗的合理组合策略.
主要方法:
- 采用了叙事审查方法.
- 对结直肠癌免疫疗法反应的新兴生物标志物进行文献搜索.
- 综合相关的临床试验,翻译研究和评论.
主要成果:
- 缺陷不匹配修复/高微卫星不稳定性 (dMMR/MSI-H) 仍然是最可靠的预测生物标志物.
- 高瘤突变负担,POLE/POLD突变和瘤微环境特征与ICI反应有关.
- 新兴生物标志物包括分子变化,抗原呈现机制,PD-L1信号,微生物组和循环瘤DNA动力学,显示MSI-H和MSSCRC的潜力.
结论:
- 在CRC中免疫治疗反应是多因素的,涉及瘤内在,免疫,微环境和系统因素.
- 整合多个生物标志物可能会增强患者分层,并指导治疗策略.
- 预期验证和标准化评估对于生物标志物的临床转化至关重要.
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