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: Shiho Chiba, Hiroaki Ikushima, Hiroshi Ueki, Hideyuki Yanai, Yoshitaka Kimura, Sho Hangai, Junko Nishio, Hideo Negishi, Tomohiko Tamura, Shinobu Saijo, Yoichiro Iwakura, Tadatsugu Taniguchi
• Journal: eLife (Elife) Vol. 3 Pg. e04177 (Aug 22 2014) ISSN: 2050-084X [Electronic] England
• PMID: 25149452 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interferon Regulatory Factors
• Irf5 protein, mouse
• Lectins, C-Type
• Polysaccharides
• RNA, Messenger
• dectin 1

Topics

• 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, metabolism)
• Macrophages (metabolism)
• Melanoma, Experimental (genetics, immunology, pathology)
• Mice, Inbred C57BL
• Models, Immunological
• Polysaccharides (chemistry, metabolism)
• Protein Binding
• RNA, Messenger (genetics, metabolism)
• Signal Transduction (immunology)