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

被引:310
作者
Munich, Stephan [1 ,4 ]
Sobo-Vujanovic, Andrea [1 ]
Buchser, William J. [1 ]
Beer-Stolz, Donna [3 ]
Vujanovic, Nikola L. [1 ,2 ]
机构
[1] Univ Pittsburgh, Dept Pathol, Inst Canc, Pittsburgh, PA 15260 USA
[2] Univ Pittsburgh, Dept Immunol, Inst Canc, Pittsburgh, PA USA
[3] Univ Pittsburgh, Dept Cell Biol & Physiol, Inst Canc, Pittsburgh, PA USA
[4] Rush Univ, Med Ctr, Dept Neurosurg, Chicago, IL 60612 USA
关键词
dendritic cells; exosomes; innate immunity; NK cells; TNF superfamily ligands; ANTICANCER EFFECTOR FUNCTION; NK CELLS; CROSS-TALK; INHIBITION; INDUCTION; RESPONSES;
D O I
10.4161/onci.20897
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 gamma(IFN gamma) 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.
引用
收藏
页码:1074 / 1083
页数:10
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