Interleukin-21 Increases Direct Cytotoxicity and IFN-γ Production of Ex Vivo Expanded NK Cells towards Breast Cancer Cells

Interleukin-21(IL-21) stimulates cytotoxicity and interferon-γ (IFN-γ) production in natural killer (NK) cells. However, little has been reported on the stimulatory effect of IL-21 on ex vivo expanded NK cells. In this study, we examined the cytotoxicity and IFN-γ production of ex vivo expanded, IL-...

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Veröffentlicht in:Anticancer research 2012-03, Vol.32 (3), p.839-846
Hauptverfasser: PARK, Young-Ki, SHIN, Dong-Jun, YOUNG JONG JEGAL, CHO, Duck, KIM, Sang-Ki, LEE, Je-Jung, SHIN, Myung-Geun, RYANG, Dong-Wook, LEE, Ji-Shin, PARK, Min-Ho, JUNG HAN YOON
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Sprache:eng
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Zusammenfassung:Interleukin-21(IL-21) stimulates cytotoxicity and interferon-γ (IFN-γ) production in natural killer (NK) cells. However, little has been reported on the stimulatory effect of IL-21 on ex vivo expanded NK cells. In this study, we examined the cytotoxicity and IFN-γ production of ex vivo expanded, IL-21-stimulated NK cells against trastuzumab-coated breast cancer cells. To expand NK cells, peripheral blood mononuclear cells (PBMCs) were isolated and co-cultured with irradiated K562-mb15-41BBL cells in the presence of IL-2 and IL-15 for 3 weeks. After a 4-day stimulation with IL-21, NK cell cytotoxicity and IFN-γ production were measured. NK cells were expanded up to median of 911-fold and represented approximately 94.93% of expanded cells after 21 days. Cytotoxicity of the expanded NK cells against the MCF-7, SKBR3, and T47D cell lines was significantly increased following 4-day stimulation with IL-21. However, antibody-dependent cellular cytotoxicity mediated by trastruzumab was significantly increased only in the SKBR3 cell line, which highly expresses the HER2/neu antigen. IL-21 pre-treatment also increased IFN-γ production in the expanded NK cells in response to the trastuzumab-coated breast cancer cells. IL-21 significantly enhances the cytolytic activity and IFN-γ production of ex vivo expanded NK cells in response to trastuzumab-coated breast cancer cells.
ISSN:0250-7005
1791-7530