Refining cancer cell death and danger signals for the improvement of immunotherapy (DECODE)

Interaction between dying cancer cells and the immune cells is crucial for eliciting productive antitumor immunity that ultimately dictates the efficacy of cancer immunotherapy. Cell deathassociated immunostimulatory signals (e.g. danger signals), clearance of cell corpses, tumor antigen availability and antigen processing/presentation by antigen-presenting cells (APCs), dictate the immunogenic and antigenic potential of dying cancer cells. However, a severe gapin-knowledge exists with regards to the exact molecular nature/composition of danger signals linked to different cancer cell death pathways induced by anticancer treatments (e.g. apoptosis, necroptosis or ferroptosis) and the mechanistic aspects of tumor antigens sensing by APCs/T cells in a cell death-context. A systematic analysis addressing these outstanding open questions is required for improving the efficacy of biomarkers-driven cancer immunotherapy. The EOS consortium DECODE strives to provide robust mechanistic and preclinical evidence to support the main hypothesis that immunogenic forms of anticancer therapy-induced cell death preserve tumor antigens and deliver a precise constellation of danger signals, which are properly decoded by the immune system thereby fostering antitumor immunity. Our major aim is to integrate the study of molecular, immunological and antigenic processes operating at the interface of dying cancer cells and immune cells, and decipher their exact relationship with antitumor immunity.