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

Record type: Article

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.

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Citation

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).

More information

Published date: 1 September 2012
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 345440
URI: http://eprints.soton.ac.uk/id/eprint/345440
ISSN: 2162-402X
PURE UUID: 8020b49e-800d-42f2-a5c4-d22b232ea16d
ORCID for Fay Chinnery: ORCID iD orcid.org/0000-0002-8082-9016
ORCID for Tim Elliott: ORCID iD orcid.org/0000-0003-1097-0222

Catalogue record

Date deposited: 20 Nov 2012 16:13
Last modified: 18 Jul 2017 05:10

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Contributors

Author: Fay Chinnery ORCID iD
Author: Catherine A King
Author: Tim Elliott ORCID iD
Author: Edward James

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