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

Elife. 2014 Aug 22:3:e04177. doi: 10.7554/eLife.04177.

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.

Keywords: Dectin-1; IRF; NK cell; immunology; innate immunity; mouse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

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

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.