Melanoma cell-derived exosomes alter macrophage and dendritic cell functions in vitro

Immunol Lett. 2012 Nov-Dec;148(1):34-8. doi: 10.1016/j.imlet.2012.07.006. Epub 2012 Aug 8.

Abstract

To clarify controversies in the literature of the field, we have purified and characterized B16F1 melanoma cell derived exosomes (mcd-exosomes) then we attempted to dissect their immunological activities. We tested how mcd-exosomes influence CD4+ T cell proliferation induced by bone marrow derived dendritic cells; we quantified NF-κB activation in mature macrophages stimulated with mcd-exosomes, and we compared the cytokine profile of LPS-stimulated, IL-4 induced, and mcd-exosome treated macrophages. We observed that mcd-exosomes helped the maturation of dendritic cells, enhancing T cell proliferation induced by the treated dendritic cells. The exosomes also activated macrophages, as measured by NF-κB activation. The cytokine and chemokine profile of macrophages treated with tumor cell derived exosomes showed marked differences from those induced by either LPS or IL-4, and it suggested that exosomes may play a role in the tumor progression and metastasis formation through supporting tumor immune escape mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Chemokines / immunology
  • Chemokines / metabolism
  • Coculture Techniques
  • Cytokines / immunology
  • Cytokines / metabolism
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Exosomes / immunology*
  • Exosomes / metabolism
  • Exosomes / ultrastructure
  • Female
  • Interleukin-4 / pharmacology
  • Lipopolysaccharides / pharmacology
  • Macrophage Activation / drug effects
  • Macrophage Activation / immunology
  • Macrophages / cytology
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Melanoma / immunology*
  • Melanoma / metabolism
  • Melanoma / pathology
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Electron, Transmission
  • NF-kappa B / immunology
  • NF-kappa B / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • Chemokines
  • Cytokines
  • Lipopolysaccharides
  • NF-kappa B
  • Interleukin-4