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

Nat Commun. 2021 Nov 18;12(1):6690. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Carcinoma, Non-Small-Cell Lung / complications
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / immunology
  • Female
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Neoplastic / immunology*
  • Humans
  • Immunophenotyping / methods*
  • Kaplan-Meier Estimate
  • Lung Neoplasms / complications
  • Lung Neoplasms / genetics
  • Lung Neoplasms / immunology
  • Macrophages / classification
  • Macrophages / immunology
  • Macrophages / metabolism
  • Male
  • Middle Aged
  • Pleural Effusion, Malignant / complications
  • Pleural Effusion, Malignant / genetics
  • Pleural Effusion, Malignant / immunology*
  • RNA-Seq / methods*
  • Single-Cell Analysis / methods*
  • T-Lymphocytes / classification
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology