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Thomas M Carroll¹, Joseph A Chadwick¹, Richard P Owen¹

¹Ludwig Institute for Cancer Research, University of Oxford, Oxford, UK.

|July 11, 2023

概括

在食道癌症中确定免疫化疗 (ICI+CTX) 患者是具有挑战性的. 高瘤单细胞含量 (TMC) 预测了更好的生存率和对ICI+CTX的反应,改善了患者的选择.

科学领域:

在瘤学瘤学.
免疫治疗是一种免疫疗法.
基因组学就是基因组学.

背景情况:

鉴定患者谁受益于免疫化疗 (ICI+CTX) 对于不可手术的食道腺癌 (EAC) 是一个重要的临床挑战.
目前在EAC中ICI+CTX疗效的预测生物标志物有限.

研究的目的:

在无法操作的EAC中识别ICI+CTX反应的预测生物标志物.
探索瘤微环境及其在ICI+CTX治疗疗效中的作用.

主要方法:

一个机会窗口试验 (LUD2015-005) 涉及35名不可手术的EAC患者,接受初始免疫检查点抑制剂 (ICI-4W) 治疗,随后进行ICI+CTX.
综合生物标志物分析,包括65000个食道癌细胞的单细胞RNA测序 (scRNA-seq).
在ICI-4W处理过程中进行多个时间点的转录基因分析.

主要成果:

一种新的T细胞炎症特征 (INCITE) 与ICI诱导的瘤缩相关.
高瘤单细胞含量 (TMC) 成为EAC患者总生存 (OS) 的ICI+CTX特异预测因子.
TMC还预测了独立队列的胃癌亚型中的ICI反应.
瘤突变负担 (TMB) 独立和附加预测了OS.

结论:

瘤单细胞含量 (TMC) 是一种新的预测生物标志物,用于ICI+CTX在胃食道癌症中的疗效.
TMC可以提高患者对新兴ICI+CTX疗法的选择.
将TMC与TMB结合起来,可以进一步优化免疫治疗的患者分层.

关键词:

细胞类型的解解.这是食道癌的癌症.免疫检查点抑制剂免疫检查点抑制剂免疫原始化免疫原始化免疫化学疗法免疫化学疗法分子造型分析 (MOP) 是一种分子造型分析.预测性的生物标志物一个单细胞RNA测序图谱与瘤相关的单细胞.瘤突变负担的突变负担

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