論文 - 詳細
| RRC ID | 32001 |
|---|---|
| 著者 | Temizoz B, Kuroda E, Ohata K, Jounai N, Ozasa K, Kobiyama K, Aoshi T, Ishii KJ. |
| タイトル | TLR9 and STING agonists synergistically induce innate and adaptive type-II IFN. |
| ジャーナル | Eur J Immunol |
| 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 Th 1-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. |
| 巻・号 | 45(4) |
| ページ | 1159-69 |
| 公開日 | 2015-4-1 |
| DOI | 10.1002/eji.201445132 |
| PMID | 25529558 |
| PMC | PMC4671267 |
| MeSH | Adjuvants, Immunologic / pharmacology Animals Cell Line, Tumor Drug Synergism Female Immunoglobulin G / biosynthesis Immunoglobulin G / immunology Interferon Regulatory Factor-3 / metabolism Interferon Regulatory Factor-7 / metabolism Interferon Type I / metabolism Interferon-gamma / biosynthesis* Interferon-gamma / immunology Interleukin-12 / metabolism Membrane Proteins / agonists* Mice Mice, Inbred C57BL Mice, Knockout Myeloid Differentiation Factor 88 / metabolism Neoplasms / therapy* Nucleotides, Cyclic / pharmacology* Oligodeoxyribonucleotides / pharmacology* T-Lymphocytes, Cytotoxic / immunology* Toll-Like Receptor 9 / agonists* |
| IF | 4.404 |
| 引用数 | 52 |
| WOS 分野 | IMMUNOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 7 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC01420 |
| ヒト・動物細胞 | B16F10(RCB2630) |