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

树突状细胞外泌体通过 TNF 超家族配体直接杀死肿瘤细胞并激活自然杀伤细胞

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

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 interferonγ (IFNγ) 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.

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