title: In vitro expanded human invariant natural killer T-cells promote functional activity of natural killer cells.
abstract: Invariant natural killer T (iNKT) cells play a pivotal role in cancer immunity through trans-activation of effector cells via swift cytokine secretion. In mice, iNKT cell activation by alpha-galactosylceramide (alpha-GC) induces potent NK cell-mediated anti-tumour effects. Here we investigated whether human iNKT cells could enhance NK cell functional activity in vitro. iNKT cell activation by alpha-GC treatment of peripheral blood mononuclear cells (PBMC) was not sufficient to enhance NK cell effector functions. However, addition of in vitro expanded iNKT cells to PBMC enhanced NK cell-mediated cytotoxicity in an alpha-GC-dependent manner. NK cell activation by iNKT cells was primarily mediated by soluble factors, and could be enhanced by the NK cell activating cytokine IL-21. These results suggest that adoptive transfer of ex vivo expanded iNKT cells will enhance NK cell function and is expected to enhance the efficacy of cancer immunotherapy, particularly in combination with IL-21 and alpha-GC.
authors: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors: María
authors: M
authors: Moreno
authors: Johan W
authors: JW
authors: Molling
authors: Silvia
authors: S
authors: von Mensdorff-Pouilly
authors: René H M
authors: RH
authors: Verheijen
authors: B Mary E
authors: BM
authors: von Blomberg
authors: Alfons J M
authors: AJ
authors: van den Eertwegh
authors: Rik J
authors: RJ
authors: Scheper
authors: Hetty J
authors: HJ
authors: Bontkes
mesh_terms: D019264:Adoptive Transfer; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D005699:Galactosylceramides / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D007378:Interleukins / Q000276:immunology*; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D000098546:Interleukin-21
chemical_list: D005699:Galactosylceramides; D007378:Interleukins; C493154:alpha-galactosylceramide; D007371:Interferon-gamma; D000098546:Interleukin-21