title: Recognition of tumor cells by Dectin-1 orchestrates innate immune cells for anti-tumor responses.
abstract: The eradication of tumor cells requires communication to and signaling by cells of the immune system. Natural killer (NK) cells are essential tumor-killing effector cells of the innate immune system; however, little is known about whether or how other immune cells recognize tumor cells to assist NK cells. Here, we show that the innate immune receptor Dectin-1 expressed on dendritic cells and macrophages is critical to NK-mediated killing of tumor cells that express N-glycan structures at high levels. Receptor recognition of these tumor cells causes the activation of the IRF5 transcription factor and downstream gene induction for the full-blown tumoricidal activity of NK cells. Consistent with this, we show exacerbated in vivo tumor growth in mice genetically deficient in either Dectin-1 or IRF5. The critical contribution of Dectin-1 in the recognition of and signaling by tumor cells may offer new insight into the anti-tumor immune system with therapeutic implications.
authors.affiliation: Department of Molecular Immunology, Institute of Industrial Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Shiho
authors.initials: S
authors.lastname: Chiba
authors.affiliation: Department of Molecular Immunology, Institute of Industrial Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ikushima
authors.affiliation: Department of Molecular Immunology, Institute of Industrial Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ueki
authors.affiliation: Department of Molecular Immunology, Institute of Industrial Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yanai
authors.affiliation: Department of Molecular Immunology, Institute of Industrial Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Kimura
authors.affiliation: Department of Molecular Immunology, Institute of Industrial Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Hangai
authors.affiliation: Department of Molecular Immunology, Institute of Industrial Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Nishio
authors.affiliation: Department of Molecular Immunology, Institute of Industrial Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Negishi
authors.affiliation: Department of Immunology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Tamura
authors.affiliation: Department of Molecular Immunology, Medical Mycology Research Center, Chiba University, Chiba, Japan.
authors.forename: Shinobu
authors.initials: S
authors.lastname: Saijo
authors.affiliation: Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.affiliation: Department of Molecular Immunology, Institute of Industrial Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Tadatsugu
authors.initials: T
authors.lastname: Taniguchi
mesh_terms: D000818:Animals; D002450:Cell Communication; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D050835:Interferon Regulatory Factors / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology; D037181:Lectins, C-Type / Q000172:deficiency / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D008546:Melanoma, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D008810:Mice, Inbred C57BL; D018448:Models, Immunological; D011134:Polysaccharides / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D000099181:Dectin-1
chemical_list: D050835:Interferon Regulatory Factors; D037181:Lectins, C-Type; D011134:Polysaccharides; D012333:RNA, Messenger; D000099181:Dectin-1; C498178:Irf5 protein, mouse
keywords: Dectin-1; IRF; NK cell; immunology; innate immunity; mouse