Innate Immune Landscape in Early Lung Adenocarcinoma by Paired Single-Cell Analyses

Cell. 2017 May 4;169(4):750-765.e17. doi: 10.1016/j.cell.2017.04.014.


To guide the design of immunotherapy strategies for patients with early stage lung tumors, we developed a multiscale immune profiling strategy to map the immune landscape of early lung adenocarcinoma lesions to search for tumor-driven immune changes. Utilizing a barcoding method that allows a simultaneous single-cell analysis of the tumor, non-involved lung, and blood cells, we provide a detailed immune cell atlas of early lung tumors. We show that stage I lung adenocarcinoma lesions already harbor significantly altered T cell and NK cell compartments. Moreover, we identified changes in tumor-infiltrating myeloid cell (TIM) subsets that likely compromise anti-tumor T cell immunity. Paired single-cell analyses thus offer valuable knowledge of tumor-driven immune changes, providing a powerful tool for the rational design of immune therapies. VIDEO ABSTRACT.

Keywords: CD141+ DC; CD1c+ DC; NK Cell; T Cell; TIM; TLS; human non-small cell lung cancer (NSCLC); immune cell atlas; lung adenocarcinoma; tumor macrophage.

MeSH terms

  • Adenocarcinoma / immunology*
  • Adenocarcinoma / pathology*
  • Adenocarcinoma of Lung
  • Dendritic Cells / pathology
  • Humans
  • Immunity, Innate*
  • Killer Cells, Natural / pathology
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / pathology*
  • Macrophages / pathology
  • Single-Cell Analysis / methods*
  • T-Lymphocytes / pathology
  • Tumor Microenvironment