{
  "abstract": "Background Glioblastoma (GBM) is an aggressive brain tumor with a poor prognosis. Only 5% of patients survive beyond five years. This dire survival rate underscores the need for improved strategies. GBM remains refractory to immunotherapy, potentially due to its immunosuppressive tumor microenvironment (TME). STING (Stimulator of Interferon Genes), which is essential for secretion of immune activating cytokines in response to some pathogens, may be a target for TME modulation in GBM. Our Lab previously showed that a small molecule STING agonist (ADU-S100), can turn on the pathway and improve survival in mouse GBM models. It is thought that STING agonists target the pathway in the stromal cells of the TME, and that the pathway is disabled in tumor cells, as a potential immunoevasion mechanism. However, our studies have shown that STING pathway components are expressed in many GBM cells. The goal of this study was to understand whether STING signaling can play a role in tumor cells and to better define that role.Methods We used western blotting, RT-qPCR, RNAseq and ELISA to examine responses to STING modulation in a panel of patient-derived GBM cell lines.Results We confirmed that STING signaling pathway components are present in GBM cell lines. Treatment with the STING agonists ADU-S100 led to activation of STING signaling as measured by Western blotting for phosphorylation of STING and downstream proteins TBK1 and NF-kB. However, secretion of cytokines was largely lacking in GBM cells, despite STING phosphorylation, indicating pathway failure. Furthermore, RNA sequencing after treatment with ADU-S100 revealed very few alterations, suggesting that the defect in STING signaling is at the transcriptional level in GBM cells, which could represent an immune evasion mechanism. Interestingly, treatment with a STING inhibitor, led to a decrease in GBM cell viability, suggesting that STING plays other roles in the biology of tumor cells.Conclusions GBM cells rewire STING signaling likely as an immune evasion mechanism. Our data shows that GBM cells can respond to STING agonists, suggesting additional functions of STING signaling which may facilitate tumor growth. These are currently under investigation.",
  "authors": [
    {
      "affiliations": [
        "Brown University, Providence, RI, USA"
      ],
      "name": "Yanfei Qiu"
    },
    {
      "affiliations": [
        "Brown University, Providence, RI, USA"
      ],
      "name": "Andrea Schmidt"
    },
    {
      "affiliations": [
        "Brown University, Providence, RI, USA"
      ],
      "name": "Sean Lawler"
    }
  ],
  "title": "943 Understanding STING signaling in glioblastoma; identifying a role for STING in tumor cells",
  "uid": "f43fefe6-927f-52d3-8cb1-7d8ec9462d47"
}