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与抗PD-1/L1疗法益处和微卫星稳定癌症的预后相关的突变负荷的特定组织值

Maishara Muquith¹, Magdalena Espinoza², Andrew Elliott³

¹Division of Hematology and Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.

|March 26, 2024

概括

免疫检查点抑制剂 (ICI) 的有效性各不相同. 瘤突变负担 (TMB) 影响微卫星稳定癌症的生存结果,在使用抗PD-1/L1疗法治疗时,在八种癌症类型中发现了特定的关联.

科学领域:

在瘤学瘤学.
免疫学免疫学免疫学
基因组学就是基因组学.

背景情况:

针对PD-1/L1的免疫检查点抑制剂 (ICI) 已在癌症治疗中取得了进展,但仅对一部分患者有益.
瘤突变负担 (TMB) 是ICI疗效的一个拟议生物标志物.
了解TMB在不同癌症中的作用对于优化免疫疗法至关重要.

研究的目的:

调查TMB与微卫星稳定癌症的生存结果之间的关联,在一个大型的现实世界队列中.
确定特定的癌症类型,其中TMB与对抗PD-1/L1疗法的反应相关.
评估通用TMB切割值对指导ICI治疗决策的有用性.

主要方法:

对现实世界临床基因组数据集的分析,包括27个组织学领域的70,698名患者.
对微卫星稳定的癌症的评估.
用抗PD-1/L1疗法治疗的患者的TMB水平与生存结果的相关性.

主要成果:

TMB证明了与生存的上下文依赖的关联,表明了利益和损害.
八种癌症类型显示TMB与抗PD-1/L1治疗改善的结果之间存在显著联系.
通过各种TMB值观察到生存益处,在某些癌症中存在剂量依赖关系.

结论:

TMB对ICI疗效的影响在很大程度上取决于癌症类型和治疗背景.
针对癌症的TMB评估比指导抗PD-1/L1治疗的通用切断值更有信息性.
组织环境对于开发强大的ICI生物标志物至关重要.

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