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The site of chemical communication between a motor neuron and a muscle fiber is called the neuromuscular junction (NMJ). The end of the motor neuron at the NMJ divides into a cluster of synaptic end bulbs. The cytoplasm of these bulbs consists of synaptic vesicles enclosing acetylcholine molecules, the principal neurotransmitter released at the NMJ. The region opposite the synaptic bulb that ends in the muscle fiber is called the motor end plate, which has acetylcholine receptors. Within the...
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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.

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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.

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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.