免疫细胞之间的串扰网络在肝细胞癌进展过程中创造了一种超越每个细胞成分功能的集体功能。
The crosstalking immune cells network creates a collective function beyond the function of each cellular constituent during the progression of hepatocellular carcinoma.
发表日期:2023 Aug 03
作者:
Nicholas Koelsch, Faridoddin Mirshahi, Hussein F Aqbi, Mulugeta Saneshaw, Michael O Idowu, Amy L Olex, Arun J Sanyal, Masoud H Manjili
来源:
Immunity & Ageing
摘要:
在肝细胞癌(HCC)的进展或抑制中,关于炎症免疫反应作用的丰富数据未能为HCC提供治愈性免疫疗法。这主要是因为专注于详细的特定细胞类型,而忽视了肝免疫系统的集体功能。为了发现集体免疫功能,我们采用系统免疫学方法,通过对DIAMOND小鼠肝脏在非酒精性脂肪肝病(NAFLD)向HCC发展过程中收集的snRNAseq数据进行高通量分析。我们报告了肝免疫细胞之间的相互信号交互以优势-劣势方式的模式,以及它们与结构细胞的相互作用,塑造出表现出细胞成分功能之外的免疫模式。这种模式发现方法认识到固有免疫细胞在NASH和HCC进展中的直接作用。这些数据表明,免疫模式的发现不仅可以检测HCC的免疫机制,尽管疾病过程中免疫细胞发生动态变化,还可以为NAFLD和HCC的治疗提供免疫调节干预手段。© 2023 Springer Nature Limited.
Abundance of data on the role of inflammatory immune responses in the progression or inhibition of hepatocellular carcinoma (HCC) has failed to offer a curative immunotherapy for HCC. This is largely because of focusing on detailed specific cell types and missing the collective function of the hepatic immune system. To discover the collective immune function, we take systems immunology approach by performing high-throughput analysis of snRNAseq data collected from the liver of DIAMOND mice during the progression of nonalcoholic fatty liver disease (NAFLD) to HCC. We report that mutual signaling interactions of the hepatic immune cells in a dominant-subdominant manner, as well as their interaction with structural cells shape the immunological pattern manifesting a collective function beyond the function of the cellular constituents. Such pattern discovery approach recognized direct role of the innate immune cells in the progression of NASH and HCC. These data suggest that discovery of the immune pattern not only detects the immunological mechanism of HCC in spite of dynamic changes in immune cells during the course of disease but also offers immune modulatory interventions for the treatment of NAFLD and HCC.© 2023. Springer Nature Limited.