Dendritic cell exosomes directly kill tumor cells and activate natural killer cells via TNF superfamily ligands

Stephan Munich, Andrea Sobo-Vujanovic, William J. Buchser, Donna Beer-Stolz, Nikola L. Vujanovic

Research output: Contribution to journalArticle

100 Scopus citations

Abstract

Autocrine and paracrine cell communication can be conveyed by multiple mediators, including membrane-associate proteins, secreted proteins and exosomes. Exosomes are 30-100 nm endosome-derived vesicles consisting in cytosolic material surrounded by a lipid bilayer containing transmembrane proteins. We have previously shown that dendritic cells (DCs) express on their surface multiple TNF superfamily ligands (TNFSFLs), by which they can induce the apoptotic demise of tumor cells as well as the activation of natural killer (NK) cells. In the present study, we demonstrate that, similar to DCs, DC-derived exosomes (DCex) express on their surface TNF, FasL and TRAIL, by which they can trigger caspase activation and apoptosis in tumor cells. We also show that DCex activate NK cells and stimulate them to secrete interferon? (IFN?) upon the interaction of DCex TNF with NK-cell TNF receptors. These data demonstrate that DCex can mediate essential innate immune functions that were previously ascribed to DCs.

Original languageEnglish
Pages (from-to)1074-1083
Number of pages10
JournalOncoImmunology
Volume1
Issue number7
DOIs
StatePublished - Dec 1 2012
Externally publishedYes

Keywords

  • Dendritic cells
  • Exosomes
  • Innate immunity
  • NK cells
  • TNF superfamily ligands

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