title: Interleukin-21 increases direct cytotoxicity and IFN-γ production of ex vivo expanded NK cells towards breast cancer cells.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Surgery, Chonnam National University Medical School, Gwangju, South Korea.
authors.forename: Young-Ki
authors.initials: YK
authors.lastname: Park
authors.forename: Dong-Jun
authors.initials: DJ
authors.lastname: Shin
authors.forename: Duck
authors.initials: D
authors.lastname: Cho
authors.forename: Sang-Ki
authors.initials: SK
authors.lastname: Kim
authors.forename: Je-Jung
authors.initials: JJ
authors.lastname: Lee
authors.forename: Myung-Geun
authors.initials: MG
authors.lastname: Shin
authors.forename: Dong-Wook
authors.initials: DW
authors.lastname: Ryang
authors.forename: Ji-Shin
authors.initials: JS
authors.lastname: Lee
authors.forename: Min-Ho
authors.initials: MH
authors.lastname: Park
authors.forename: Jung Han
authors.initials: JH
authors.lastname: Yoon
authors.forename: Young Jong
authors.initials: YJ
authors.lastname: Jegal
mesh_terms: D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D007378:Interleukins / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology*; D000098546:Interleukin-21
chemical_list: D007378:Interleukins; D007371:Interferon-gamma; D000098546:Interleukin-21