title: Distinct roles for the NK cell-activating receptors in mediating interactions with dendritic cells and tumor cells.
abstract: NK cells are innate immune cells that are important in tumor immunity, but also have the ability to modulate the adaptive immune system through cytokine production or direct cell-cell interactions. This study investigates the interaction of NK cells with dendritic cells (DCs) and tumor cells, and the role of specific NK cell-activating receptors in this process. Primary rat NK cells and an NK cell line produced IFN-γ when cocultured with either DCs or the rat hepatoma cell line McA-RH7777 (McA). This NK cell activation by DCs and McA required cell-cell contact and was dependent on distinct NK-activating receptors. Silencing NK cell expression of NKp46 and NKp30 significantly diminished DC- and McA-mediated NK cell IFN-γ production, respectively. NK cells killed immature and mature DCs independently of NKp46, NKp30, and NKG2D; however, cytotoxicity against McA cells was dependent on NKp30 and NKG2D. Thus, we have shown in this study that NKp30 plays dual activating roles in NK-McA tumor interactions by mediating cytokine production and cytotoxicity. More importantly, NK cells are activated by both DCs and hepatoma cells to produce IFN-γ, but require distinct NK cell-activating receptors, NKp46 and NKp30, respectively. Our data suggest that therapeutics could be developed specifically to target NK-DC interactions without compromising NK tumor immunity.
authors.affiliation: Division of Transplantation and Program in Immunology, Department of Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Lu-En
authors.initials: LE
authors.lastname: Wai
authors.forename: Jordan A
authors.initials: JA
authors.lastname: Garcia
authors.forename: Olivia M
authors.initials: OM
authors.lastname: Martinez
authors.forename: Sheri M
authors.initials: SM
authors.lastname: Krams
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002450:Cell Communication / Q000276:immunology*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018920:Coculture Techniques; D003601:Cytotoxicity Tests, Immunologic; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000096:biosynthesis; D037181:Lectins, C-Type / Q000502:physiology*; D008114:Liver Neoplasms, Experimental / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D055655:NK Cell Lectin-Like Receptor Subfamily K; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000502:physiology*; D055628:Natural Cytotoxicity Triggering Receptor 3 / Q000502:physiology*; D009363:Neoplasm Proteins / Q000502:physiology*; D051381:Rats; D011917:Rats, Inbred Lew; D011971:Receptors, Immunologic / Q000502:physiology*; D015534:Trans-Activators / Q000502:physiology*
chemical_list: D037181:Lectins, C-Type; D055655:NK Cell Lectin-Like Receptor Subfamily K; C113208:NKR-P2 protein, rat; D055627:Natural Cytotoxicity Triggering Receptor 1; D055628:Natural Cytotoxicity Triggering Receptor 3; C495388:Ncr1 protein, rat; C513306:Ncr3 protein, rat; D009363:Neoplasm Proteins; D011971:Receptors, Immunologic; D015534:Trans-Activators; D007371:Interferon-gamma