Antigen presentation enhancement via immunogenic cell death

Antigen presentation enhancement via immunogenic cell death describes the process by which certain modalities of regulated cell death in tumor cells (induced by chemotherapeutic agents, radiotherapy, or immune cytotoxicity) generate cellular debris rich in DAMPs and tumor antigens, thereby acting as potent stimuli for antigen-presenting cells—primarily dendritic cells—which process and present these antigens to T cells. This leads to the activation and expansion of tumor-specific cytotoxic T lymphocytes that can seek and destroy remaining malignant cells. ICD is characterized by the exposure of calreticulin at the plasma membrane, release of ATP and HMGB1, and subsequent maturation and recruitment of dendritic cells. The process is central to both the efficacy of some cancer therapies and the design of cancer vaccines, but is not itself a molecular drug target; rather, it is a desirable immunologic outcome manipulated by targeting upstream molecular pathways or through combinational therapies.

Other names

Immunogenic cell death-mediated antigen presentationICD-induced antigen presentation

Agents trigger ICD in tumor cells, leading to the exposure/release of DAMPs (calreticulin, ATP, HMGB1), which act as "eat-me" and "find-me" signals for antigen-presenting cells. These signals facilitate phagocytosis, dendritic cell maturation, and subsequent cross-presentation of tumor antigens to T cells, prompting anti-tumor immunity. ICD activates various forms of regulated cell death including necroptosis (RIPK3-MLKL pathway), pyroptosis (CASP1/CASP11, gasdermin D), and ferroptosis. DAMP-mediated activation of PRRs (pattern recognition receptors) such as TLR4, P2X7, CD91 on APCs