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Publication : Extrinsic Phagocyte-Dependent STING Signaling Dictates the Immunogenicity of Dying Cells.

First Author  Ahn J Year  2018
Journal  Cancer Cell Volume  33
Issue  5 Pages  862-873.e5
PubMed ID  29706455 Mgi Jnum  J:261862
Mgi Id  MGI:6156728 Doi  10.1016/j.ccell.2018.03.027
Citation  Ahn J, et al. (2018) Extrinsic Phagocyte-Dependent STING Signaling Dictates the Immunogenicity of Dying Cells. Cancer Cell 33(5):862-873.e5
abstractText  The ability of dying cells to activate antigen-presenting cells (APCs) is carefully controlled to avoid unwarranted inflammatory responses. Here, we show that engulfed cells containing cytosolic double-stranded DNA species (viral or synthetic) or cyclic di-nucleotides (CDNs) are able to stimulate APCs via extrinsic STING (stimulator of interferon genes) signaling, to promote antigen cross-presentation. In the absence of STING agonists, dying cells were ineffectual in the stimulation of APCs in trans. Cytosolic STING activators, including CDNs, constitute cellular danger-associated molecular patterns (DAMPs) only generated by viral infection or following DNA damage events that rendered tumor cells highly immunogenic. Our data shed insight into the molecular mechanisms that drive appropriate anti-tumor adaptive immune responses, while averting harmful autoinflammatory disease, and provide a therapeutic strategy for cancer treatment.
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