DAMPs in the immunogenicity of cell death

Abstract

Damage-associated molecular patterns (DAMPs) are endogenous molecules-such as proteins, lipids, and nucleic acids-released or exposed during cellular injury or stress, which shape immune responses by engaging danger sensors on the cell surface or within the cell interior. Recent advances have elucidated molecular links between distinct cell death pathways-apoptosis, necroptosis, pyroptosis, and ferroptosis-and DAMP release, emphasizing how biochemical features (e.g., posttranslational modifications) and temporal dynamics influence immunogenic versus tolerogenic outcomes. Here, we summarize these mechanisms, including both immunostimulatory and immunosuppressive DAMPs, and review key DAMP receptors-such as TLRs, NLRs, cGAS, and advanced glycosylation end-product-specific receptor (AGER)/RAGE-along with their downstream signaling cascades. Finally, we highlight emerging strategies to modulate DAMP signaling for cancer immunotherapy and the treatment of inflammatory diseases.

Keywords: DAMP receptors; DAMPs; ICD; cell death; immunotherapy.