| First Author | Curran E | Year | 2016 |
| Journal | Cell Rep | Volume | 15 |
| Issue | 11 | Pages | 2357-66 |
| PubMed ID | 27264175 | Mgi Jnum | J:238247 |
| Mgi Id | MGI:5818647 | Doi | 10.1016/j.celrep.2016.05.023 |
| Citation | Curran E, et al. (2016) STING Pathway Activation Stimulates Potent Immunity against Acute Myeloid Leukemia. Cell Rep 15(11):2357-66 |
| abstractText | Type I interferon (IFN), essential for spontaneous T cell priming against solid tumors, is generated through recognition of tumor DNA by STING. Interestingly, we observe that type I IFN is not elicited in animals with disseminated acute myeloid leukemia (AML). Further, survival of leukemia-bearing animals is not diminished in the absence of type I IFN signaling, suggesting that STING may not be triggered by AML. However, the STING agonist, DMXAA, induces expression of IFN-beta and other inflammatory cytokines, promotes dendritic cell (DC) maturation, and results in the striking expansion of leukemia-specific T cells. Systemic DMXAA administration significantly extends survival in two AML models. The therapeutic effect of DMXAA is only partially dependent on host type I IFN signaling, suggesting that other cytokines are important. A synthetic cyclic dinucleotide that also activates human STING provided a similar anti-leukemic effect. These data demonstrate that STING is a promising immunotherapeutic target in AML. |
