Molecular Profiling and Functional Analysis of Macrophage-Derived Tumor Extracellular Vesicles

Cell Rep. 2019 Jun 4;27(10):3062-3080.e11. doi: 10.1016/j.celrep.2019.05.008.


Extracellular vesicles (EVs), including exosomes, modulate multiple aspects of cancer biology. Tumor-associated macrophages (TAMs) secrete EVs, but their molecular features and functions are poorly characterized. Here, we report methodology for the enrichment, quantification, and proteomic and lipidomic analysis of EVs released from mouse TAMs (TAM-EVs). Compared to source TAMs, TAM-EVs present molecular profiles associated with a Th1/M1 polarization signature, enhanced inflammation and immune response, and a more favorable patient prognosis. Accordingly, enriched TAM-EV preparations promote T cell proliferation and activation ex vivo. TAM-EVs also contain bioactive lipids and biosynthetic enzymes, which may alter pro-inflammatory signaling in the cancer cells. Thus, whereas TAMs are largely immunosuppressive, their EVs may have the potential to stimulate, rather than limit, anti-tumor immunity.

Keywords: T cell response; exosome; extracellular vesicle; inflammation; lipid metabolism; lipidomics; proteomics; tumor microenvironment; tumor-associated macrophage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / therapeutic use
  • Bone Marrow Cells / cytology
  • Cell Line, Tumor
  • Cell Proliferation
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Extracellular Vesicles / metabolism*
  • Female
  • Interleukin-4 / pharmacology
  • Lipopolysaccharides / pharmacology
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Protein Interaction Maps
  • Proteome / analysis
  • Proteomics
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Th1 Cells / cytology
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Transplantation, Homologous


  • Antibodies
  • Csf1r protein, mouse
  • Lipopolysaccharides
  • Proteome
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
  • Interleukin-4