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European Journal of Immunology
Article . 2015 . Peer-reviewed
License: CC BY NC ND
Data sources: Crossref
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European Journal of Immunology
Article
License: CC BY NC ND
Data sources: UnpayWall
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PubMed Central
Other literature type . 2015
License: CC BY NC ND
Data sources: PubMed Central
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TLR9 and STING agonists synergistically induce innate and adaptive type‐II IFN

Authors: Burcu Temizoz; Ken Ishii; Keiichi Ohata; Etsushi Kuroda; Taiki Aoshi; Koji Ozasa; Nao Jounai; +1 Authors

TLR9 and STING agonists synergistically induce innate and adaptive type‐II IFN

Abstract

Agonists for TLR9 and Stimulator of IFN Gene (STING) act as vaccine adjuvants that induce type‐1 immune responses. However, currently available CpG oligodeoxynucleotide (ODN) (K‐type) induces IFNs only weakly and STING ligands rather induce type‐2 immune responses, limiting their potential therapeutic applications. Here, we show a potent synergism between TLR9 and STING agonists. Together, they make an effective type‐1 adjuvant and an anticancer agent. The synergistic effect between CpG ODN (K3) and STING‐ligand cyclic GMP–AMP (cGAMP), culminating in NK cell IFN‐γ (type‐II IFN) production, is due to the concurrent effects of IL‐12 and type‐I IFNs, which are differentially regulated by IRF3/7, STING, and MyD88. The combination of CpG ODN with cGAMP is a potent type‐1 adjuvant, capable of inducing strong Th1‐type responses, as demonstrated by enhanced antigen‐specific IgG2c and IFN‐γ production, as well as cytotoxic CD8+ T‐cell responses. In our murine tumor models, intratumoral injection of CpG ODN and cGAMP together reduced tumor size significantly compared with the singular treatments, acting as an antigen‐free anticancer agent. Thus, the combination of CpG ODN and a STING ligand may offer therapeutic application as a potent type‐II IFN inducer.

Related Organizations
Keywords

Mice, Knockout, Interferon Regulatory Factor-7, Membrane Proteins, Drug Synergism, Interleukin-12, Innate Immunity, Mice, Inbred C57BL, Interferon-gamma, Mice, Adjuvants, Immunologic, Oligodeoxyribonucleotides, Cell Line, Tumor, Immunoglobulin G, Neoplasms, Interferon Type I, Myeloid Differentiation Factor 88, Animals, Female, Interferon Regulatory Factor-3, Nucleotides, Cyclic, T-Lymphocytes, Cytotoxic

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    citations
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
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    influence
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    impulse
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    Top 1%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
129
Top 1%
Top 10%
Top 1%
Green
hybrid
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