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Viral antigen mediated NKp46 activation of NK cells results in tumor rejection via NK-DC crosstalk.
MedLine Citation:
PMID:  23162755     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
Fay Chinnery; Catherine A King; Tim Elliott; Andrew R Bateman; Edward James
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Publication Detail:
Type:  JOURNAL ARTICLE    
Journal Detail:
Title:  Oncoimmunology     Volume:  1     ISSN:  2162-402X     ISO Abbreviation:  Oncoimmunology     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-11-19     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101570526     Medline TA:  Oncoimmunology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  874-883     Citation Subset:  -    
Affiliation:
Cancer Sciences Unit; Faculty of Medicine; University of Southampton; Southampton, UK.
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