Targeting immunogenic cell death in cancer

• Published in: Molecular oncology Vol. 14; no. 12; pp. 2994 - 3006
• Main Authors: Ahmed, Asma, Tait, Stephen W.G.
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.12.2020; John Wiley and Sons Inc
• Subjects: Adaptive immunity; Adenosine triphosphate; Alarmins - metabolism; AMP; Animals; Apoptosis; BAX protein; Bcl-x protein; Calreticulin; cancer; caspase; Cell death; Cell survival; Chemokines; CXCL10 protein; Cyclic GMP; DAMPs; Dendritic cells; Endoplasmic reticulum; Endoplasmic Reticulum Stress; FADD protein; FasL protein; FLIP protein; HMGB1 protein; Humans; Immunity - immunology; Immunogenic Cell Death; Immunogenicity; Interferon; Kinases; Lipopolysaccharides; Lymphocytes B; Lymphoma; Major histocompatibility complex; Mitochondrial DNA; Mobility; Necroptosis; Neoplasms - immunology; Neoplasms - pathology; PD-L1 protein; Photodynamic therapy; Protein kinase; Protein-serine/threonine kinase; Reactive oxygen species; Review; T-Lymphocytes - immunology; Therapeutic targets; Toll-like receptors; Tumor necrosis factor-TNF; cancer; cell death; interferon; immunogenic cell death; DAMPs; caspase
• ISSN: 1574-7891; 1878-0261; 1878-0261
• DOI: 10.1002/1878-0261.12851

Immunogenic cell death (ICD) is a form of cell death that can engage immunity. Therapeutic engagement of ICD in cancer may lead to more effective responses by eliciting antitumor immunity. Here, we discuss various modalities of ICD, highlighting our current understanding of the molecular basis of ICD. Finally, we outline the potential and challenge of harnessing ICD in cancer immunotherapy. 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 in vivo. 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.