title: Immunomodulation of inducible co-stimulator (ICOS) in human cytokine-induced killer cells against cholangiocarcinoma through ICOS/ICOS ligand interaction.
abstract: OBJECTIVE
  To evaluate the immunomodulation of inducible co-stimulator (ICOS) in cytokine-induced killer (CIK) cells against cholangiocarcinoma.
  
  
  METHODS
  CIK cells were generated from normal peripheral blood mononuclear cells. Methyl thiazolyl tetrazolium assay was performed to assess proliferation of CIK-ICOS and controlled CIK cells; ELISA was used to analyze the expression of cytokines. Reverse transcription-polymerase chain reaction and immunohistochemistry were performed to evaluate the expression of ICOS ligand (ICOSL) in CIK cells and human cholangiocarcinoma cell line QBC939 cells. The cytotoxicity of CIK cells was determined either by lactate dehydrogenase-releasing assay in vivo or alteration of tumor size prior to and after the treatment of CIK cells in vivo.
  
  
  RESULTS
  CIK-ICOS cells proliferated more and expressed higher secretion a level of interferon-γ than the controlled CIK. These cells exhibited higher cytotoxicity against cholangiocarcinoma cell lines at all efficacy: toxicity (E:T) ratios tested than the controlled CIK cells. More importantly, the anti-ICOSL antibody was able to attenuate the elevated cytotoxicity mediated by ICOS overexpression. When injected into cholangiocarcinoma xenografts in severe combined immunodeficiency mice, CIK-ICOS cells survived better than the controlled CIK cells around xenografts and significantly reduced the growth rate of cholangiocarcinoma, with least volume increase and more severe necrosis of the xenografts than controlled mice treated with saline, CIK or CIK-enhanced green fluorescent protein.
  
  
  CONCLUSIONS
  ICOS can enhance the cytotoxic effect of CIK cells against cholangiocarcinoma both in vitro and in vivo. This effect is mediated by ICOS-augmented cytokine secretion and cell proliferation, and in part through ICOS-ICOSL interaction.
authors.affiliation: Department of General Surgery, Renji Hospital, Shanghai, China.
authors.forename: Min
authors.initials: M
authors.lastname: He
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Wei Jin
authors.initials: WJ
authors.lastname: Shi
authors.forename: Shu Jun
authors.initials: SJ
authors.lastname: Wang
authors.forename: Hui Fang
authors.initials: HF
authors.lastname: Sha
authors.forename: Jiu Xian
authors.initials: JX
authors.lastname: Feng
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D001650:Bile Duct Neoplasms / Q000276:immunology / Q000628:therapy*; D001653:Bile Ducts, Intrahepatic; D045744:Cell Line, Tumor; D018281:Cholangiocarcinoma / Q000276:immunology / Q000628:therapy*; D055612:Cytokine-Induced Killer Cells / Q000276:immunology*; D006801:Humans; D060945:Inducible T-Cell Co-Stimulator Ligand / Q000502:physiology*; D060889:Inducible T-Cell Co-Stimulator Protein / Q000502:physiology*; D051379:Mice
chemical_list: C556692:ICOS protein, human; C498514:ICOSLG protein, human; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein