Single-cell analysis of diverse immune phenotypes in malignant pleural effusion.

Single-cell analysis of diverse immune phenotypes in malignant pleural effusion.
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恶性胸腔积液中多种免疫表型的单细胞分析

DOI:
10.1038/s41467-021-27026-9
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发表时间:
2021-11-18
影响因子:
16.6
通讯作者:
Shi HZ
Shi HZ
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Huang ZY;Shao MM;Zhang JC;Yi FS;Du J;Zhou Q;Wu FY;Li S;Li W;Huang XZ;Zhai K;Shi HZ

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不同免疫细胞之间复杂的相互作用在恶性胸腔积液(MPE)的发生发展中起着重要作用。在这里,我们对来自非小细胞肺癌诱导的MPE患者的62,382个细胞进行单细胞RNA测序,以描述MPE中浸润免疫细胞的组成、谱系和功能状态。与血液中相应的免疫细胞相比,MPE中的免疫细胞显示出许多转录特征,这些转录特征富集于调节性T细胞、B细胞、巨噬细胞和树突状细胞。辅助T、细胞毒性T、调节性T和T滤泡辅助细胞表达多个免疫检查点或共刺激分子。细胞-细胞相互作用分析发现,与CD8+ T细胞相比,调节性B细胞与CD4+ T细胞的相互作用更多。巨噬细胞具有转录异质性,符合M2极化特征。此外,MPE中的免疫细胞表现出与缺氧微环境相关的糖酵解途径的普遍上调。这些发现显示了人类MPE中免疫细胞的详细图谱,并增强了对晚期非小细胞肺癌潜在诊断和治疗靶点的理解。人肺(恶性胸腔积液)MPE的详细免疫细胞亚群鉴定对诊断和预后具有重要意义。在这里,作者使用单细胞RNA测序来鉴定MPE内的免疫细胞类型,并显示与血液中循环免疫细胞相比的差异基因表达。
The complex interactions among different immune cells have important functions in the development of malignant pleural effusion (MPE). Here we perform single-cell RNA sequencing on 62,382 cells from MPE patients induced by non-small cell lung cancer to describe the composition, lineage, and functional states of infiltrating immune cells in MPE. Immune cells in MPE display a number of transcriptional signatures enriched for regulatory T cells, B cells, macrophages, and dendritic cells compared to corresponding counterparts in blood. Helper T, cytotoxic T, regulatory T, and T follicular helper cells express multiple immune checkpoints or costimulatory molecules. Cell-cell interaction analysis identifies regulatory B cells with more interactions with CD4+ T cells compared to CD8+ T cells. Macrophages are transcriptionally heterogeneous and conform to M2 polarization characteristics. In addition, immune cells in MPE show the general up-regulation of glycolytic pathways associated with the hypoxic microenvironment. These findings show a detailed atlas of immune cells in human MPE and enhance the understanding of potential diagnostic and therapeutic targets in advanced non-small cell lung cancer. Detailed immune cell subset identification in human lung (malignant pleural effusion) MPE is important for diagnosis and prognosis. Here the authors use single cell RNA sequencing to identify immune cell types within MPE and show differential gene expression compared to circulating immune cells in blood.
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