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在COVID-19微环境中改变的ACE2和干扰素格局与固体瘤中的抗PD-1反应相关

Karthikeyan Subbarayan¹, Ahmed Al-Samadi^2,3, Helene Schäfer¹

¹Medical Faculty, Martin Luther University Halle-Wittenberg, Magdeburger Str. 2, 06112, Halle (Saale), Germany.

Cellular and molecular life sciences : CMLS

|December 3, 2024

概括

瘤中的 ангиотензин转化酶-2 (ACE2) 表达影响免疫反应和宿主免疫性. 准ACE2诱导的干扰素编程死亡连接体1 (IFN-PD-L1) 轴可能会降低癌症患者的COVID-19严重程度.

科学领域:

免疫学免疫学免疫学
病毒学病毒学
在瘤学瘤学.

背景情况:

ангиотензин转化酶-2 (ACE2) 是SARS-CoV-2的细胞受体.
在瘤中ACE2的作用和临床相关性,特别是在COVID-19患者中,仍未得到充分研究.
感染SARS-CoV-2的瘤患者经常经历较差的结果.

研究的目的:

分析ACE2在瘤中的表达,功能和临床相关性.
研究ACE2表达对免疫反应相关分子和机制的影响.
探索针对COVID-19癌症患者ACE2通路的潜在治疗策略.

主要方法:

分析瘤和邻近组织的RNA测序数据,以及COVID-19患者的全血.
在和实验分析 (qPCR,流细胞测量,西部斑点,RNA-seq) 的ACE2和免疫分子在瘤细胞系和内皮细胞与不同的ACE2表达水平.
与ACE2表达细胞和外周血液单核细胞共同培养实验.

主要成果:

高ACE2细胞显示HLA类I的调节的mRNA和/或蛋白质水平,编程死亡连接体1 (PD-L1),抗原处理机器 (APM) 组件和干扰素 (IFN) 信号通路.
与高ACE2细胞共同培养增加了免疫细胞迁移,透,亡,先天免疫细胞因子释放,并改变了NK细胞介导的细胞毒性.
在各种模型系统和SARS-CoV-2感染时,ACE2表达与改变宿主免疫性相关.

结论:

ACE2表达显著影响瘤免疫性和免疫细胞相互作用.
由ACE2诱导的IFN-PD-L1轴代表了减轻癌症患者COVID-19严重性的潜在治疗目标.
这些发现为ACE2在免疫反应中的作用提供了新的见解,并建议在瘤患者中管理SARS-CoV-2感染的策略.

关键词:

免疫逃脱是为了逃脱免疫.免疫反应的免疫反应.免疫治疗是一种免疫疗法.这就是SARS-CoV-2病毒.瘤这些瘤

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