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

Background/Aim: Interleukin-21(IL-21) stimulates cytotoxicity and interferon-gamma (IFN-gamma) 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-gamma 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-gamma production were measured. Results: NK cells were expanded up to median of 91 I-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-gamma production in the expanded NK cells in response to the trustuzumab-coated breast cancer cells. Conclusion: IL-21 significantly enhances the cytolytic activity and IFN-gamma production of ex vivo expanded NK cells in response to trastuzumab-coated breast cancer cells.