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

Zhong-Yin Huang,Wei Li,Xian-Zhen Huang,Huan-Zhong Shi,Jian-Chu Zhang,Kan Zhai,Feng-Shuang Yi,Ming-Ming Shao,Sha Li,Juan Du,Feng-Yao Wu,Qiong Zhou

doi:10.1038/s41467-021-27026-9

Abstract

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.

Highlights

The complex interactions among different immune cells have important functions in the development of malignant pleural effusion (MPE)
Given that neutrophils are the predominant type of leukocytes in blood, whereas lymphocytes are the predominant type of immune cells in MPE, we excluded polynuclear cells from our scRNA-seq analysis and focused on mononuclear cells
The 19 expression groups were grouped by hierarchical clustering, leading to the characterization of major cellular compartments of T cells, B cells, natural killer (NK) cells, and myeloid cells, with the most abundant MPE immune cells being T cells (Fig. 1c–e and Supplementary Fig. 1c)

Summary

Introduction

The complex interactions among different immune cells have important functions in the development of malignant pleural effusion (MPE). By using single-cell RNA sequencing (scRNA-seq) technique, the landscape of infiltrating immune cells has been demonstrated in non-small cell lung cancer (NSCLC)[16,17], hepatocellular carcinoma[18,19], head and neck squamous cell carcinoma[20], breast cancer[21,22], and other tumors. These studies have shown that the activation of B cells, increase in Treg cells, decrease in cytotoxic T cells, and the enrichment of exhausted T cells are the immune characteristics of the solid tumor microenvironment. This study identifies the cellular and biological features that are specific to MPE and describes the different immune status from the primary tumor

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