STING is an intracellular protein expressed in antigen-presenting cells (APCs), such as dendritic cells (DCs) and macrophages, as well as other cell types.1,2
STING is an innate immune activator that stimulates APCs to drive cytotoxic T-cell activity.2
It is triggered when an intracellular-sensing protein detects DNA from pathogens or dying tumor cells.3,4
Activation of STING leads to the production and secretion of proinflammatory cytokines that increase antitumor immunity, such as interferons (IFNs) and tumor necrosis factor alpha (TNFα).3,5
IFNs promote tumor inflammation by stimulating APCs to activate T cells, initiating T-cell proliferation and trafficking to the tumor microenvironment. 6,8
IFNs can also amplify the antitumor function of natural killer (NK) and cytotoxic T cells, as well as promote memory T-cell survival.2,9,10
STING can also stimulate activation of the NLRP3 (nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 3) inflammasome, leading to the production of additional cytokines.11
Barber GN. STING-dependent cytosolic DNA sensing pathways. Trends Immunol. 2014;35(2):88-93.
Corrales L, McWhirter SM, Dubensky TW Jr, Gajewski TF. The host STING pathway at the interface of cancer and immunity. J Clin Invest. 2016;126(7):2404-2411.
Corrales L, Gajewski TF. Molecular pathways: targeting the stimulator of interferon genes (STING) in the immunotherapy of cancer. Clin Cancer Res. 2015;21(21):4774-4779.
Woo S-R, Fuertes MB, Corrales L, et al. STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors. Immunity. 2014;41(5):830-842.
Curran E, Chen X, Corrales L, et al. STING pathway activation stimulates potent immunity against acute myeloid leukemia. Cell Rep. 2016;15(11):2357-2366.
Corrales L, Glickman LH, McWhirter SM, et al. Direct activation of STING in the tumor microenvironment leads to potent and systemic tumor regression and immunity. Cell Rep. 2015;11(7):1018-1830.
Woo S-R, Corrales L, Gajewski TF. The STING pathway and the T cell-inflamed tumor microenvironment. Trends Immunol. 2015;36(4):250-256.
Ohkuri T, Ghosh A, Kosaka A, et al. STING contributes to anti-glioma immunity via triggering type-I IFN signals in the tumor microenvironment. Cancer Immunol Res. 2014;2(12):1199-1208.
Swann JB, Hayakawa Y, Zerafa N, et al. Type I IFN contributes to NK cell homeostasis, activation, and antitumor function. J Immunol. 2007;178(12):7540-7549.
Zitvogel L, Galluzzi L, Kepp O, Smyth MJ, Kroemer G. Type I interferons in anticancer immunity. Nat Rev Immunol. 2015;15(7):405-414.
Gaidt MM, Ebert TS, Chauhan D, et al. The DNA inflammasome in human myeloid cells is initiated by a STING-cell death program upstream of NLRP3. Cell. 2017;171(5):1110-1124.
Song S, Peng P, Tang Z, et al. Decreased expression of STING predicts poor prognosis in patients with gastric cancer. Sci Rep. 2017;7:39858. doi:10.1038/srep39858.
Xia T, Konno H, Ahn J, Barber GN. Deregulation of STING signaling in colorectal carcinoma constrains DNA damage responses and correlates with tumorigenesis. Cell Rep. 2016;14(2):282-297.
Xia T, Konno H, Barber GN. Recurrent loss of STING signaling in melanoma correlates with susceptibility to viral oncolysis. Cancer Res. 2016;76(22):6747-6759.
Fu J, Kanne DB, Leong M, et al. STING agonist formulated cancer vaccines can cure established tumors resistant to PD-1 blockade. Sci Transl Med. 2015;7(283):283ra52. doi:10.1126/scitranslmed.aaa4306.
Ghaffari A, Peterson N, Khalaj K, et al. STING agonist therapy in combination with PD-1 immune checkpoint blockade enhances response to carboplatin chemotherapy in high-grade serous ovarian cancer. Br J Cancer. 2018;119(4):440-449.
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