RRC ID 67668
Author Chiba S, Ikushima H, Ueki H, Yanai H, Kimura Y, Hangai S, Nishio J, Negishi H, Tamura T, Saijo S, Iwakura Y, Taniguchi T.
Title Recognition of tumor cells by Dectin-1 orchestrates innate immune cells for anti-tumor responses.
Journal Elife
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.
Volume 3
Pages e04177
Published 2014-8-22
DOI 10.7554/eLife.04177
PMID 25149452
PMC PMC4161974
MeSH Animals Cell Communication Cell Line, Tumor Cell Proliferation Cytotoxicity, Immunologic Dendritic Cells / metabolism Gene Expression Regulation, Neoplastic HEK293 Cells Humans Immunity, Innate / immunology* Interferon Regulatory Factors / metabolism Killer Cells, Natural / immunology Lectins, C-Type / deficiency Lectins, C-Type / metabolism* Macrophages / metabolism Melanoma, Experimental / genetics Melanoma, Experimental / immunology* Melanoma, Experimental / pathology* Mice, Inbred C57BL Models, Immunological Polysaccharides / chemistry Polysaccharides / metabolism Protein Binding RNA, Messenger / genetics RNA, Messenger / metabolism Signal Transduction / immunology
IF 7.08
DNA material CSII-EF-MCS-IRES2-Venus (RDB04384) pCMV-VSV-G-RSV-Rev (RDB04393)
Human and Animal Cells HeLa A549(RCB0098) HCT116(RCB2979) MKN45(RCB1001) PC-3(RCB2145) K562(RCB1897) B16F1(RCB2649) B16F10(RCB2630) LLC(RCB0558)