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对免疫检查点阻塞疗法反应的代谢预测因子

Ofir Shorer¹, Keren Yizhak^1,2

¹Department of Cell Biology and Cancer Science, The Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa 3525422, Israel.

|November 15, 2023

概括

瘤微环境 (TME) 中的免疫细胞代谢会影响癌症患者对免疫检查点抑制剂 (ICI) 的反应. 这项研究揭示了与ICI治疗反应相关的不同代谢状态,使其成为患者结果的预测指标.

科学领域:

免疫学免疫学免疫学
代谢学代谢学代谢学
癌症研究癌症研究

背景情况:

瘤微环境 (TME) 中的免疫细胞代谢对于预测患者对免疫检查点抑制剂 (ICI) 的反应至关重要.
目前缺乏接受ICI治疗的患者TME中免疫细胞的详细代谢表征.
了解这些代谢特征对于改善癌症治疗策略至关重要.

研究的目的:

用ICI治疗的癌症患者的TME中免疫细胞的代谢的特征.
为了确定与患者对ICI治疗的反应相关的代谢状态.
开发基于免疫细胞代谢的ICI治疗结果的预测模型.

主要方法:

对大约1700个代谢基因进行了半监督分析.
利用来自大约230个癌症患者样本的100多万个免疫细胞的单细胞RNA测序数据.
基于代谢基因表达特征的免疫细胞的聚类.

主要成果:

在免疫细胞内识别出不同的代谢状态,独立于它们的免疫状态.
发现了与患者对ICI反应显著相关的特定代谢状态.
开发了一种使用12个基因签名的预测模型,可以在各种癌症类型中准确地区分响应者和非响应者 (AUC = 0.8-0.92).

结论:

在TME内的免疫细胞代谢是患者对ICI反应的强有力的指标.
代谢剖析为预测ICI治疗疗效提供了一个有希望的途径.
这项研究为开发新的生物标志物和针对癌症代谢的治疗策略提供了基础.

关键词:

癌症癌症癌症癌症人类新陈代谢的人类新陈代谢.免疫学免疫学免疫学

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