Immu-31. Dysfunctional Sting Pathway Signaling Compromises Innate Immunity in Glioblastoma
Year: 2018
Type: article
Abstract: Stimulator of interferon genes (STING), a protein located in the endoplasmic reticulum, is a key mediator of innate immune response to non-CpG cytosolic DNA. Intact STING has been shown to be involved in the induction of the innate antitumor response in Glioblastoma (GBM). Upon sensing cytosolic dsDNA, the STING pathway is activated, resulting in phosphorylation of interferon regulatory factor 3 (IRF3), which leads to the induction of a type I interferon response, essential for innate immunity. Recent evidence shows the STING pathway is dysregulated in other cancers. Western analysis on several glioblastoma derived cell lines, showed that STING was present at variable levels in 6 out of 7 cell lines. In addition, the dsDNA sensor cGAS, a protein upstream of STING, was expressed in only 3 out of 7 cell lines. Cell lines were treated with a variety of innate agonists including CpG free dsDNA construct to test the activation of the STING pathway. We observed a variable response to the dsDNA stimulus. The M059J cell line exhibited an intact STING pathway with activation of pIRF3 and pSTAT1 (a marker of IFN production). Both LN18 and T98G cell lines failed to activate pIRF3 and pSTAT1, whereas A172 cells showed activated pSTAT1 in the absence of pIRF3. This data suggests the STING Pathway is dysregulated in glioblastoma cell lines and highlights a potential mechanism of evasion of innate immune signaling in glioblastoma. Ongoing studies will examine the mechanism of this dysregulation and its impact on innate therapies such as PVSRIPO.
Source: Neuro-Oncology
Institutions: Duke Medical Center, Duke University
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2899669141