title: Allogeneic and xenogeneic anti-tumor effect of callithrix jacchus natural killer cells is dependent on NKp30 and B7-H6 interaction.
abstract: Natural Killer (NK) cells mount a fast and efficient immune response against tumor cells and are currently a major focus in the development of anti-cancer cell-based therapies. Due to major differences between the murine and human NK cell receptor system, a non-human primate model would be helpful to evaluate the efficiency of NK-cell based therapies prior to clinical applications. In humans, B7-H6 has been shown to facilitate the elimination of lymphoma cells through the interaction with its receptor NKp30. The common marmoset (Callithrix jacchus) is a new world monkey readily used in biomedical research due to its easy management and proximity to humans. In this study, we demonstrated the expression of B7-H6 antigen in marmoset B-lymphoblastoid cell lines. In addition, a method was established to isolate B- or NK-cells from peripheral blood of marmosets with purities of up to 97%We detected the expression of B7-H6 in lymphoma cells and for the first time in leukemic blasts of human acute myeloid leukemia (AML). Marmoset NK cells were shown to lyse marmoset B lymphoblastoid cell line (B-LCL) cells by up to 28.4% and human B-LCL cells by up to 20%. This effect was abrogated when the NK cells were pre-treated with an anti-NKp30 specific antibody. Also, marmoset NK cells were able to lyse primary leukemic AML cells and lymphoma cells by up to 8.3 and 20.3%respectively. Stimulation of marmoset NK cells with recombinant B7-H6 induced phosphorylation of ERK1/2 and proliferation rates. Furthermore, the secretion of IL-1β, IL-8, IFN-γ and TNF-α was significantly increased upon B7-H6 stimulation. In conclusion, we demonstrated that non-human primate NK cells have similar mechanisms for the lysis of tumor cells as human NK cells. Thus, this animal model constitutes a very promising tool for the development and evaluation of novel NK-cell based therapies.
authors.affiliation: Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Müller
authors.affiliation: Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Schlahsa
authors.affiliation: Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany.
authors.forename: H J
authors.initials: HJ
authors.lastname: Zhang
authors.affiliation: Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany.
authors.forename: Y
authors.initials: Y
authors.lastname: Skaik
authors.affiliation: Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Eiz-Vesper
authors.affiliation: Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Immenschuh
authors.affiliation: Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Blasczyk
authors.affiliation: Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Figueiredo
mesh_terms: D000818:Animals; D060887:B7 Antigens / Q000276:immunology*; D002144:Callithrix; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D015470:Leukemia, Myeloid, Acute / Q000276:immunology*; D016393:Lymphoma, B-Cell / Q000276:immunology*; D020935:MAP Kinase Signaling System / Q000276:immunology; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000276:immunology; D048052:Mitogen-Activated Protein Kinase 3 / Q000276:immunology; D055628:Natural Cytotoxicity Triggering Receptor 3 / Q000276:immunology*
chemical_list: D060887:B7 Antigens; C431710:NCR3 protein, human; C542363:NCR3LG1 protein, human; D055628:Natural Cytotoxicity Triggering Receptor 3; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3