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

eLife

Tomohiko Tamura¹  Junko Nishio¹  Hiroaki Ikushima¹  Hideyuki Yanai¹  Yoichiro Iwakura²  Yoshitaka Kimura³  Shinobu Saijo³  Sho Hangai⁴  Hideo Negishi⁴  Tadatsugu Taniguchi⁴  Shiho Chiba⁴  Hiroshi Ueki⁴ 

[1] Center for International Research on Integrative Biomedical Systems, Institute of Industrial Science, The University of Tokyo, Tokyo, Japan;Japan Science and Technology Agency, Core Research for Evolution Science and Technology, Tokyo, Japan;Max Planck-The University of Tokyo Center for Integrative Inflammology, Tokyo, Japan;Department of Molecular Immunology, Institute of Industrial Science, The University of Tokyo, Tokyo, Japan;

关键词: innate immunity;    Dectin-1;    NK cell;    IRF;   

DOI  :  10.7554/eLife.04177

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown