BACKGROUND/AIM: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND/AIM: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: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.
Authors: Sofya A Erokhina; Maria A Streltsova; Leonid M Kanevskiy; William G Telford; Alexander M Sapozhnikov; Elena I Kovalenko Journal: Immunol Cell Biol Date: 2017-12-19 Impact factor: 5.126
Authors: Juliane Wagner; Viktoria Pfannenstiel; Anja Waldmann; Judith W J Bergs; Boris Brill; Sabine Huenecke; Thomas Klingebiel; Franz Rödel; Christian J Buchholz; Winfried S Wels; Peter Bader; Evelyn Ullrich Journal: Front Immunol Date: 2017-06-12 Impact factor: 7.561