Abstract
Immunogenic cell death (ICD) is a type of cancer cell death triggered by certain chemotherapeutic drugs, oncolytic viruses, physicochemical therapies, photodynamic therapy, and radiotherapy. It involves the activation of the immune system against cancer in immunocompetent hosts. ICD comprises the release of damage-associated molecular patterns (DAMPs) from dying tumor cells that result in the activation of tumor-specific immune responses, thus eliciting long-term efficacy of anticancer drugs by combining direct cancer cell killing and antitumor immunity. Remarkably, subcutaneous injection of dying tumor cells undergoing ICD has been shown to provoke anticancer vaccine effects invivo. DAMPs include the cell surface exposure of calreticulin (CRT) and heat-shock proteins (HSP70 and HSP90), extracellular release of adenosine triphosphate (ATP), high-mobility group box-1 (HMGB1), type I IFNs and members of the IL-1 cytokine family. In this review, we discuss the cell death modalities connected to ICD, the DAMPs exposed during ICD, and the mechanism by which they activate the immune system. Finally, we discuss the therapeutic potential and challenges of harnessing ICD in cancer immunotherapy.
Highlights
Immunogenic cell death (ICD) is a form of regulated cell death (RCD) that is sufficient to activate an adaptive immune response in an immunocompetent setting [1]
ICD encompasses the release of damage-associated molecular patterns (DAMPs) from dying tumor cells, that are recognized by innate pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs) and NOD-like receptors (NLRs) resulting in the activation of tumor-specific immune responses, provoking long-term efficacy of anticancer drugs by combining direct cancer cell killing and antitumor immunity, generally associated with immunological memory [1,2]
Accumulating evidence clearly underscored the ability of DAMPs released from dying cells to activate specific antitumor immune responses
Summary
Immunogenic cell death (ICD) is a form of regulated cell death (RCD) that is sufficient to activate an adaptive immune response in an immunocompetent setting [1] It has been classified as a distinct poorly defined entity induced by certain chemotherapeutic drugs, oncolytic viruses, physicochemical therapies, photodynamic therapy, and radiotherapy [1,2]. ICD encompasses the release of DAMPs from dying tumor cells, that are recognized by innate pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs) and NOD-like receptors (NLRs) resulting in the activation of tumor-specific immune responses, provoking long-term efficacy of anticancer drugs by combining direct cancer cell killing and antitumor immunity, generally associated with immunological memory [1,2]. We discuss future perspectives for therapeutic targeting of ICD in cancer therapy
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