Viral antigen mediated NKp46 activation of NK cells results in tumor rejection via NK-DC crosstalk


Chinnery, Fay, King, Catherine A, Elliott, Tim, Bateman, Andrew R and James, Edward (2012) Viral antigen mediated NKp46 activation of NK cells results in tumor rejection via NK-DC crosstalk Oncolmmunology, 1, (6), pp. 874-883. (doi:10.4161/onci.20636). (PMID:23162755).

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Description/Abstract

Natural killer (NK) cells play a critical role in antitumor immunity, their activation being regulated through NK cell receptors. Although the endogenous ligands for these receptors are largely unknown, viral ligands have been identified. We investigated the ability of an activating NK receptor ligand derived from the mumps virus, haemagglutinin-neuraminidase (HN) to enhance NK activation against tumor cells. HN-expressing B16.OVA tumor cells induced stronger activation of NK cells compared with B16.OVA cells and also promoted dendritic cell (DC) activation toward a DC1 phenotype, in vitro. Moreover, incubation of DCs, NK cells and HN-expressing B16-OVA cells further enhanced NK cell activation through the NK-DC crosstalk, in a cell-to-cell contact- and IL-12-dependent fashion. Immunization of mice with HN-expressing B16-OVA cells resulted in > 85% survival rate after subsequent challenge with parental B16 or B16.OVA tumor cells. Tumor rejection was dependent on both NK and CD8+ T cells but not on CD4+ T cells, demonstrating induction of an effective adaptive immune response through innate immune cell activation. Our data indicate the potential of using robust NK cell activation, which through the NK-DC crosstalk stimulates effective antitumor responses, providing an alternate vaccine strategy.

Item Type: Article
Digital Object Identifier (DOI): doi:10.4161/onci.20636
ISSNs: 2162-402X (print)
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Organisations: Cancer Sciences
ePrint ID: 345440
Date :
Date Event
1 September 2012Published
Date Deposited: 20 Nov 2012 16:13
Last Modified: 17 Apr 2017 16:21
Further Information:Google Scholar
URI: http://eprints.soton.ac.uk/id/eprint/345440

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