Reframing cell death: Unveiling interactions and synergistic mechanisms in tumor immunity

Cell death is a well-coordinated process that encompasses apoptosis as well as other mechanisms, including pyroptosis, autophagic cell death, ferroptosis and necroptosis. These modalities are hierarchically stratified by combined metabolic and inflammatory stress signals, as well as by integrating molecular hubs that program disease-specific immune fate. The role that a cell plays within the tumour microenvironment (TME) is determined by combined signaling of metabolic stress, inflammation, and mitochondrial disruption. These signals are intercepted by central nodes like the caspase-GSDM axis, RIPK complexes and the cGAS–STING pathway to confer instructive plasticity on cell death.