Inflammatory cell death in cancer: linking pyroptosis, necroptosis, ferroptosis, PANoptosis, and antitumor immunity

Inflammatory cell death has emerged as a critical interface between cancer therapy and antitumor immunity. Unlike relatively non-inflammatory cell death, pyroptosis, necroptosis, ferroptosis, and PANoptosis can generate or release damage-associated molecular patterns (DAMPs), tumor antigens, inflammatory cytokines, oxidized lipids, and nucleic acid ligands that reshape the tumor microenvironment. These death programs link therapeutic stress to dendritic cell activation, antigen cross-presentation, type I interferon signaling, cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) signaling, and cytotoxic T-cell responses. However, their immune consequences are highly context dependent. Preclinical studies suggest that selected inflammatory cell death pathways may improve responses to immune checkpoint blockade under defined experimental conditions; however, these effects vary with tumor type, cellular context, and treatment modality, and their clinical relevance remains to be established. Conversely, ferroptosis or PANoptosis in suppressive myeloid cells can reinforce immune evasion. This review summarizes recent experimental advances connecting inflammatory cell death with tumor immunity, focusing on molecular executors, immune mediators, therapeutic opportunities, biomarkers, and translational challenges. We propose that future cancer therapy should move beyond simply inducing tumor cell death toward designing immune-productive death programs that are spatially controlled, cell-type selective, and rationally synchronized with immunotherapy.