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

Publication date: Available online 26 April 2018
Source:Cancer Cell
Author(s): Jeonghyun Ahn, Tianli Xia, Ailem Rabasa Capote, Dillon Betancourt, Glen N. Barber
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.

Graphical abstract

Teaser

Ahn et al. show that dying tumor cells that contain STING-dependent adjuvants activate STING signaling in engulfing macrophages to trigger immune responses, cross-presentation of antigens, and generation of cytotoxic T cells, providing a potential cancer therapeutic strategy.


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