Back to Search
Start Over
TLR9 and STING agonists synergistically induce innate and adaptive type-II IFN.
- Source :
- European Journal of Immunology; Apr2015, Vol. 45 Issue 4, p1159-1169, 11p
- Publication Year :
- 2015
-
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 T<subscript>h</subscript>1-type responses, as demonstrated by enhanced antigen-specific IgG2c and IFN-γ production, as well as cytotoxic CD8<superscript>+</superscript> 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00142980
- Volume :
- 45
- Issue :
- 4
- Database :
- Complementary Index
- Journal :
- European Journal of Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 101947801
- Full Text :
- https://doi.org/10.1002/eji.201445132