Immunogenic cell death induction pathways

Immunogenic cell death induction pathways refer to cellular processes where dying cells emit molecular signals (DAMPs) that activate the immune system, mainly through dendritic cell maturation and priming of T-cell responses against antigens released by dying cells[1][2]. ICD can be triggered by certain chemotherapeutics, radiotherapy, photodynamic therapy, and some viruses, resulting in antitumor immunity[1][2][4][5]. The underlying mechanisms involve regulated stress, especially endoplasmic reticulum stress, the release/exposure of DAMPs (e.g., calreticulin, ATP, HMGB1, HSP70/90), and downstream activation of pattern recognition pathways in immune cells[2][3]. ICD encompasses several sub-forms including apoptosis, necroptosis, pyroptosis, ferroptosis, and cuproptosis[3][4]. These pathways are exploited in cancer therapy to stimulate immune-mediated tumor clearance, often serving as a mechanism for the "in situ vaccination" effect[1][2][4].\n\nNotable clarification: "Immunogenic cell death induction pathways" is not a canonical drug target (such as a receptor, enzyme, or transporter), but rather a collective term for regulated cell death modalities that result in immune activation. For molecularly-targeted information, one should specify individual targets or effectors involved (e.g., calreticulin, HMGB1, TLR4, eIF2α, etc.)[2][3][5].

Other names

Immunogenic cell death (ICD)Immunogenic apoptosis

Induction of ER stress in target cells; Promotion of release/exposure of damage-associated molecular patterns (DAMPs) such as calreticulin (CRT), ATP, HMGB1, HSP70/HSP90; Triggering adaptive immune response by antigen presentation through dendritic cells; Activation of pattern recognition receptors (e.g., TLR2/4, purinergic receptors, cGAS); Caspase-dependent and caspase-independent death modalities (apoptosis, necroptosis, pyroptosis, ferroptosis)