Recognition of tumor cells by Dectin-1 orchestrates innate immune cells for anti-tumor responses

• Published in: eLife Vol. 3; p. e04177
• Main Authors: Chiba, Shiho, Ikushima, Hiroaki, Ueki, Hiroshi, Yanai, Hideyuki, Kimura, Yoshitaka, Hangai, Sho, Nishio, Junko, Negishi, Hideo, Tamura, Tomohiko, Saijo, Shinobu, Iwakura, Yoichiro, Taniguchi, Tadatsugu
• Format: Journal Article
• Language: English
• Published: England eLife Sciences Publications Ltd 22-08-2014; eLife Sciences Publications, Ltd
• Subjects: Animals; Cell Communication; Cell Line, Tumor; Cell Proliferation; Cytotoxicity, Immunologic; Dectin-1; Dendritic cells; Dendritic Cells - metabolism; Effector cells; Flow cytometry; Gene Expression Regulation, Neoplastic; HEK293 Cells; Humans; Immune system; Immunity, Innate - immunology; Immunology; Innate immunity; Interferon Regulatory Factors - metabolism; IRF; Killer Cells, Natural - immunology; Lectins, C-Type - deficiency; Lectins, C-Type - metabolism; Ligands; Lungs; Macrophages; Macrophages - metabolism; Melanoma; Melanoma, Experimental - genetics; Melanoma, Experimental - immunology; Melanoma, Experimental - pathology; Metastasis; Mice, Inbred C57BL; Models, Immunological; Natural killer cells; NK cell; Polysaccharides - chemistry; Polysaccharides - metabolism; Protein Binding; RNA, Messenger - genetics; RNA, Messenger - metabolism; Rodents; Science; Signal Transduction - immunology; Transcription activation; Transcription factors; Tumor cells; mouse; Dectin-1; innate immunity; IRF; immunology; NK cell
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.04177

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.