The article discusses the role of STING (stimulator of interferon genes) in the detection and response to microbial agents, autoinflammatory diseases, and cancer. STING is a signaling molecule found in the endoplasmic reticulum that plays a crucial role in initiating innate immune responses to cytosolic DNA or cyclic dinucleotides (CDNs). The discovery of the STING pathway has provided insights into the mechanisms of innate immunity and autoimmunity, as well as potential therapeutic targets for treating autoinflammatory diseases and cancer. Key points include: 1. **STING Activation**: STING is activated by CDNs produced by bacteria or cGAS, which binds to cytosolic DNA. This activation leads to the production of type I interferons and pro-inflammatory cytokines. 2. **Autoinflammatory Diseases**: STING signaling is implicated in various autoinflammatory diseases, such as systemic lupus erythematosus (SLE) and Aicardi-Goutières syndrome (AGS), where mutations in *TMEM173* (encoding STING) can lead to hyperactivity of the STING pathway. 3. **Cancer**: STING signaling is essential for antitumor immune responses, promoting the production of cytokines and type I interferons that can enhance T cell responses and prevent tumor growth. 4. **Post-Translational Modifications**: STING can be phosphorylated and ubiquitinated, which regulates its activity and stability. 5. **STING and Microorganisms**: STING is activated by DNA viruses, retroviruses, and certain bacteria, contributing to host defense against these pathogens. 6. **STING and RNA Viruses**: STING is also involved in the suppression of RNA virus replication, possibly through mechanisms that regulate viral RNA translation or post-translational modifications. 7. **STING and Mitochondrial DNA**: Leaky mitochondrial DNA can activate STING, but caspases may prevent this from occurring during apoptosis. 8. **STING in Cancer**: STING signaling is important for radiation-induced and spontaneous natural antitumor T cell responses, and STING agonists have shown antitumor activity in animal studies. The article concludes that understanding the role of STING in innate immunity and cancer can lead to the development of novel therapies, including immunotherapies and vaccines.The article discusses the role of STING (stimulator of interferon genes) in the detection and response to microbial agents, autoinflammatory diseases, and cancer. STING is a signaling molecule found in the endoplasmic reticulum that plays a crucial role in initiating innate immune responses to cytosolic DNA or cyclic dinucleotides (CDNs). The discovery of the STING pathway has provided insights into the mechanisms of innate immunity and autoimmunity, as well as potential therapeutic targets for treating autoinflammatory diseases and cancer. Key points include: 1. **STING Activation**: STING is activated by CDNs produced by bacteria or cGAS, which binds to cytosolic DNA. This activation leads to the production of type I interferons and pro-inflammatory cytokines. 2. **Autoinflammatory Diseases**: STING signaling is implicated in various autoinflammatory diseases, such as systemic lupus erythematosus (SLE) and Aicardi-Goutières syndrome (AGS), where mutations in *TMEM173* (encoding STING) can lead to hyperactivity of the STING pathway. 3. **Cancer**: STING signaling is essential for antitumor immune responses, promoting the production of cytokines and type I interferons that can enhance T cell responses and prevent tumor growth. 4. **Post-Translational Modifications**: STING can be phosphorylated and ubiquitinated, which regulates its activity and stability. 5. **STING and Microorganisms**: STING is activated by DNA viruses, retroviruses, and certain bacteria, contributing to host defense against these pathogens. 6. **STING and RNA Viruses**: STING is also involved in the suppression of RNA virus replication, possibly through mechanisms that regulate viral RNA translation or post-translational modifications. 7. **STING and Mitochondrial DNA**: Leaky mitochondrial DNA can activate STING, but caspases may prevent this from occurring during apoptosis. 8. **STING in Cancer**: STING signaling is important for radiation-induced and spontaneous natural antitumor T cell responses, and STING agonists have shown antitumor activity in animal studies. The article concludes that understanding the role of STING in innate immunity and cancer can lead to the development of novel therapies, including immunotherapies and vaccines.