基于PD-1检查点封锁的全瘤基因组生物标志物
Razvan Cristescu1, Robin Mogg2, Mark Ayers2
1Merck & Co., Kenilworth, NJ 07033, USA. razvan_cristescu@merck.com.
概括
瘤突变负担 (TMB) 和T细胞炎症基因表达特征 (GEP) 预测了像布罗利祖马布这样的PD-1免疫疗法的反应. 这些独特的生物标志物可以识别可能受益于免疫治疗的患者,有助于临床试验的设计.
科学领域:
- 免疫疗法
- 癌症学
- 基因组学
背景情况:
- 编程细胞死亡蛋白-1 (PD-1) 和编程细胞死亡配体-1 (PD- L1) 检查点阻断免疫疗法具有持久的抗瘤作用.
- 然而,并非所有癌症患者都能接受这种治疗.
研究的目的:
- 评估瘤突变负荷 (TMB) 和T细胞炎症基因表达特征 (GEP) 对勃利祖马布反应的预测效用.
- 调查TMB和GEP在识别响应者和不响应者之间的相关性.
主要方法:
- 来自四个KEYNOTE临床试验的22种瘤类型的300多名患者样本的分析.
- 评估癌症基因组图谱 (TCGA) 数据库的生物标志物相关性.
- 关节分层分析以确定生物标志物定义的耐药性模式.
主要成果:
- TMB和T细胞炎症的GEP共同预测了PD-1抗体的反应.
- TMB和GEP都是独立预测反应的.
- TMB和GEP的相关性很低,表明它们具有不同的生物特征.
结论:
- TMB和GEP是有价值的生物标志物,用于识别会对PD-1阻断免疫治疗有反应的患者.
- 这些生物标志物可以为选择合适的免疫治疗方案 (单疗或组合疗法) 提供临床试验设计信息.
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