title: The host STING pathway at the interface of cancer and immunity.
abstract: A major subset of human cancers shows evidence for spontaneous adaptive immunity, which is reflected by the presence of infiltrating CD8+ T cells specific for tumor antigens within the tumor microenvironment. This observation has raised the question of which innate immune sensing pathway might detect the presence of cancer and lead to a natural adaptive antitumor immune response in the absence of exogenous infectious pathogens. Evidence for a critical functional role for type I IFNs led to interrogation of candidate innate immune sensing pathways that might be triggered by tumor presence and induce type I IFN production. Such analyses have revealed a major role for the stimulator of IFN genes pathway (STING pathway), which senses cytosolic tumor-derived DNA within the cytosol of tumor-infiltrating DCs. Activation of this pathway is correlated with IFN-β production and induction of antitumor T cells. Based on the biology of this natural immune response, pharmacologic agonists of the STING pathway are being developed to augment and optimize STING activation as a cancer therapy. Intratumoral administration of STING agonists results in remarkable therapeutic activity in mouse models, and STING agonists are being carried forward into phase I clinical testing.
authors.forename: Leticia
authors.initials: L
authors.lastname: Corrales
authors.forename: Sarah M
authors.initials: SM
authors.lastname: McWhirter
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Dubensky
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Gajewski
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000970:Antineoplastic Agents / Q000494:pharmacology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D003600:Cytosol / Q000378:metabolism; D004273:DNA, Neoplasm / Q000032:analysis; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D016899:Interferon-beta / Q000276:immunology; D007372:Interferons / Q000276:immunology*; D051379:Mice; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism*; D059016:Tumor Microenvironment / Q000276:immunology
chemical_list: D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D016899:Interferon-beta; D007372:Interferons