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.
Highlights
In recent years, our understanding of innate immune recognition of microbial components and its critical role in host defense against infection has grown considerably
Within the interferon regulatory factors (IRFs) family of transcription factors, several members including IRF3, IRF5 and IRF7 are well-known for the pivotal roles they serve in the innate immune receptor-mediated gene induction programme (Honda and Taniguchi, 2006)
Since the marked B16 lung metastasis was not observed in mice deficient in T and B lymphocyte development (Figure 1—figure supplement 2B), we examined the contribution of IRF5 in anti-tumor innate immune response, wherein Natural killer (NK) cells are best known for their direct anti-tumor cytotoxicity (Smyth et al, 2002)
Summary
Our understanding of innate immune recognition of microbial components and its critical role in host defense against infection has grown considerably. Upon recognition of PAMPs, these receptors activate NF-κB, interferon regulatory factors (IRFs) and other transcription factors, which induce the transcription of cognate target genes (Tamura et al, 2008; Ikushima et al, 2013). This results in the evocation of innate immune responses that instruct subsequent innate immune responses. Dead or injured cells recruit and activate innate inflammatory cells in the absence of infection through recognition by PRRs of released self-derived molecules termed damage-associated molecular patterns (DAMPs) (Bianchi, 2007; Rubartelli and Lotze, 2007). The role of innate immune receptors in anti-tumor innate immune response is unknown
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
