Immunogenic Cell Death Pathway (ICD)

Immunogenic cell death (ICD) is a specific form of regulated cell death that elicits an adaptive immune response against antigens from the dying cell. Unlike non-immunogenic forms of cell death, ICD actively stimulates the immune system to recognize and attack cells—most notably cancer cells—by releasing or exposing immunostimulatory molecules known as damage-associated molecular patterns (DAMPs). The most critical DAMPs involved in ICD include Calreticulin (CRT), Heat Shock Proteins (HSP70/HSP90), High Mobility Group Box 1 protein (HMGB1), and Adenosine Triphosphate (ATP). ICD involves several interconnected signaling modules: An ER stress module centered around phosphorylation of eIF2α, an apoptotic module involving caspase-8 activation, and an exocytosis module requiring actin cytoskeleton dynamics for vesicular trafficking of DAMPs. Inducers of ICD are being developed both alone or combined with other therapies (e.g., chemotherapy, radiotherapy) to enhance anti-tumor vaccination strategies. Successful induction leads not only to immediate tumor clearance but also long-term immunological memory against cancer recurrence. ICD contrasts sharply with tolerogenic forms of cell death that may promote immune evasion by tumors.

Various, depending on the specific ICD inducer; involves induction of ER stress, caspase activation, and DAMP release.