Platelet STING agonism and venous thrombosis: translational implications for improved disease outcomes
Year: 2023
Type: article
Abstract: Protective host innate and adaptive immune responses to insult by pathogens and oncogenesis are multicomponent and multifaceted in nature, with excessive and/or sustained inflammatory responses leading to untoward consequences. An expanding body of literature supports the importance of the cGAS (cyclic GMP-AMP synthase)/stimulator of interferon genes (STING) pathway, a cytosolic DNA-sensing pathway promoting production of type I interferons and proinflammatory cytokines/chemokines, in the effectiveness of protective host responses against infectious disease and cancer.1,2 STING is a transmembrane protein localized to the endoplasmic reticulum, which functions as an adaptor protein in the cGAS–STING pathway.3 Recognition of cytoplasmic viral/tumor DNA by cGAS leads to the generation of cyclic guanosine monophosphate–adenosine monophosphate (cGAMP) that activates STING protein, leading to its subsequent posttranslational modification, multimerization, and the subcellular translocation of STING complexes for organelle-associated functionality.1,2 STING activation by cGAMP or synthetic STING agonists is classically associated with the cGAS/STING–TBK1–IRF3 type 1 IFN signaling cascade linked to the suppression of viral replication/infection and to the reinforcement of a proinflammatory tissue microenvironment supportive of greater disease control.2
Source: Journal of Leukocyte Biology
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Awards: Targeting the Chemokine System to Sensitize Tumors to Immunotherapy, NCI ETCTN Pittsburgh Cancer Consortium (PCC), Immune Exclusion in Cancer Immunotherapy, Vaccine Targeting of RCC Blood Vessels to Promote TME Normalization and Enhance TIL Recruitment, Melanoma and Skin Cancer Program SPORE, Cancer Center Support Grant
OpenAlex ID: W4382919129