STING Pathway Activation Stimulates Potent Immunity Against Acute Myeloid Leukemia

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2016 Jun 7

PMID 27264175

Citations 91

Authors

Emily Curran

Xiufen Chen

Leticia Corrales

Douglas E Kline

Thomas W Dubensky Jr

Priyanka Duttagupta

Marcin Kortylewski

Justin Kline

Affiliations

Soon will be listed here.

Abstract

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-β 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.

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