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膜局部化的新抗原预测了癌症免疫疗法的疗效

Zoe Goldberger¹, Sylvie Hauert², Kevin Chang²

¹Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, USA; Department of Bioengineering, McGill University, Montreal, QC, Canada.

Cell reports. Medicine

|August 8, 2023

概括

预测对免疫检查点免疫疗法 (ICI) 的反应至关重要. 这项研究发现,位于细胞膜上的新抗原显著改善了对ICI治疗患者反应的预测.

科学领域:

在瘤学瘤学.
免疫学免疫学免疫学
计算生物学计算生物学

背景情况:

免疫检查点免疫疗法 (ICI) 通过重新激活抗瘤免疫反应,在癌症治疗中表现有前途.
然而,只有少数患者对ICI有反应,这凸显了对预测生物标志物的需求.
瘤突变负担 (TMB) 是一个已知的预测因素,但它的准确性可以得到改进.

研究的目的:

研究新抗原亚细胞局部化在预测ICI反应中的作用.
确定是否将新抗原定位与TMB结合起来可以提高预测能力.

主要方法:

对小鼠黑色素瘤模型的分析.
从1,722名用ICI治疗的患者的临床数据进行了回顾性分析.
评估新抗原的亚细胞局部化 (特别是膜结合) 和TMB.

主要成果:

较高比例的膜局部化新抗原,特别是在血膜,与ICI响应度相关.
在人类数据集中,在多种癌症类型中观察到这种相关性.
结合膜局部化和TMB分析,改善了对ICI患者反应的预测.

结论:

新抗原的细胞下定位,特别是膜的存在,是ICI反应的重要因素.
将膜新抗原分析与TMB集成为预测ICI疗效提供了更强大的方法.
这些发现可以为选择患者接受ICI治疗的临床指南提供信息.

关键词:

生物标志物生物标志物癌症癌症癌症癌症癌症细胞膜的细胞膜.免疫疗法免疫疗法新抗原是一种新抗原.瘤突变负担的突变负担

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