Tumor cells infected with oncolytic influenza A virus prime natural killer cells for lysis of resistant tumor cells.

Ogbomo, Henry and Michaelis, Martin and Geiler, Janina and van Rikxoort, Marijke and Muster, Thomas and Egorov, Andrej and Doerr, Hans Wilhelm and Cinatl, Jindrich (2010) Tumor cells infected with oncolytic influenza A virus prime natural killer cells for lysis of resistant tumor cells. Medical Microbiology and Immunology, 199 (2). pp. 93-101. ISSN 1432-1831. (doi:https://doi.org/10.1007/s00430-009-0139-0) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

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Official URL
http://dx.doi.org/10.1007/s00430-009-0139-0

Abstract

Tumor resistance to lysis by resting natural killer (NK) cells may be overcome by priming of NK cells with cytokines or by binding of NK activating receptors to ligands expressed on target cells. In this study, major histocompatibility complex class I (MHC-I)-negative LNCaP and MHC-I-positive DU145 cells were infected with genetically modified influenza A virus lacking the non-structural gene 1 (NS1 IAV). The cells were used to investigate the influence of NS1 IAV infection on NK cell lysis of tumor cells as well as to prime NK cells for lysis of LNCaP and DU145 cells. While LNCaP cells infected with DeltaNS1 IAV showed enhanced lysis when compared with mock-infected cells (93% +/- 1.47 vs. 52% +/- 0.74), both mock-infected and DeltaNS1 IAV-infected DU145 cells were resistant to NK cell lysis. Moreover, NK cells primed with DeltaNS1 IAV-infected LNCaP/DU145 cells effectively lysed resistant DU145 and sensitive LNCaP cells to a greater extent than NK cells primed with mock-infected LNCaP/DU145 or non-primed NK cells. Also, NK cell priming with DeltaNS1 IAV-infected tumor cells enhanced extracellular signal-regulated kinase phosphorylation and increased granule release in NK cells. The increased granule release was specifically mediated by NKp46, which eventually potentiated NK cells primed with DeltaNS1 IAV-infected tumor cells to overcome the inhibitory effects posed by MHC-I expression on DU145 cells. These findings show that in addition to direct lytic activity of NK cells, DeltaNS1 IAV may influence anti-tumoral responses by priming NK cells.

Item Type: Article
Subjects: Q Science > QR Microbiology > QR180 Immunology
Q Science > QR Microbiology > QR355 Virology
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Martin Michaelis
Date Deposited: 05 Jun 2013 19:24 UTC
Last Modified: 30 Apr 2014 10:27 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/34070 (The current URI for this page, for reference purposes)
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