Single-cell RNA sequencing demonstrates the molecular and cellular reprogramming of metastatic lung adenocarcinoma

Nat Commun. 2020 May 8;11(1):2285. doi: 10.1038/s41467-020-16164-1.


Advanced metastatic cancer poses utmost clinical challenges and may present molecular and cellular features distinct from an early-stage cancer. Herein, we present single-cell transcriptome profiling of metastatic lung adenocarcinoma, the most prevalent histological lung cancer type diagnosed at stage IV in over 40% of all cases. From 208,506 cells populating the normal tissues or early to metastatic stage cancer in 44 patients, we identify a cancer cell subtype deviating from the normal differentiation trajectory and dominating the metastatic stage. In all stages, the stromal and immune cell dynamics reveal ontological and functional changes that create a pro-tumoral and immunosuppressive microenvironment. Normal resident myeloid cell populations are gradually replaced with monocyte-derived macrophages and dendritic cells, along with T-cell exhaustion. This extensive single-cell analysis enhances our understanding of molecular and cellular dynamics in metastatic lung cancer and reveals potential diagnostic and therapeutic targets in cancer-microenvironment interactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Adenocarcinoma of Lung / blood supply
  • Adenocarcinoma of Lung / genetics*
  • Adenocarcinoma of Lung / immunology
  • Adenocarcinoma of Lung / pathology
  • Cell Lineage
  • Cellular Reprogramming / genetics*
  • Disease Progression
  • Endothelial Cells / pathology
  • Humans
  • Ligands
  • Lung Neoplasms / blood supply
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / immunology
  • Lung Neoplasms / pathology
  • Myeloid Cells / pathology
  • Myofibroblasts / pathology
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Neovascularization, Pathologic / pathology
  • Phenotype
  • Receptors, Cell Surface / metabolism
  • Sequence Analysis, RNA*
  • Single-Cell Analysis*
  • Stromal Cells / metabolism
  • Survival Analysis


  • Ligands
  • Receptors, Cell Surface