Stimulator of interferon genes (STING) can promote tumor inflammation and antitumor immunity. STING activation can promote increased T-cell activation and inflammation in the tumor microenvironment.
- STING is an intracellular protein expressed in antigen-presenting cells (APCs), such as dendritic cells (DCs) and macrophages, as well as other cell types1,2
- STING is an innate immune activator that stimulates APCs to drive cytotoxic T-cell activity2
- It is triggered when an intracellular-sensing protein detects DNA from pathogens or dying tumor cells3,4
- 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-cellproliferation and trafficking to the tumor microenvironment6,8
- IFNs can also amplify the antitumor function of natural killer (NK) and cytotoxic T cells, as well as promote memory T-cell survival2,9,10
- 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 cytokines11
- Preclinical data suggest that activation of STING can increase
T-cellpriming, leading to increased T-cellactivation and an inflamed tumor microenvironment4,6-8
- Furthermore, mouse models indicate that activation of STING along with blockade of immune checkpoint receptors may synergistically promote the antitumor immune response15,16
1. Barber GN. STING-dependent cytosolic DNA sensing pathways. Trends Immunol. 2014;35(2):88-93. 2. 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. 3. 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. 4. 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. 5. Curran E, Chen X, Corrales L, et al. STING pathway activation stimulates potent immunity against acute myeloid leukemia. Cell Rep.