The nucleic acid sensor STING is an important regulator in innate immune cells to protect the body against invading pathogens and malignant cells. Currently, synthetic STING agonists are tested in clinical trials for their ability to induce a de novo antitumor immune response in metastatic tumour patients. Besides activating immune cells, we discovered that STING agonists can induce cell death in both cancer and immune cells, although at different concentration ranges. In preliminary experiments, we discovered that some cancer cells die via the immunogenic cell death pathway. Understanding if and how STING induces immunogenic cancer cell death and activates immune cells while maintaining their viability will be crucial. For this project, we will investigate which pathways regulate STING induced cell death in cancer and immune cells using CRISPR, proteomics and high throughput drug screening platforms. Determine if the identified cell death pathways are immune activating or immune silent and test which of these pathways are differentially regulated in cancer and immune cells.