Immunogenic cell death,DAMPs and anticancer therapeutics: An emerging amalgamation |
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Authors: | Abhishek D. Garg Dominika Nowis Jakub Golab Peter Vandenabeele Dmitri V. Krysko Patrizia Agostinis |
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Affiliation: | 1. Department of Molecular Cell Biology, Catholic University of Leuven, Belgium;2. Department of Immunology, Center of Biostructure, Medical University of Warsaw, Poland;3. Molecular Signalling and Cell Death Unit, Department for Molecular Biomedical Research, VIB, Belgium;4. Department of Molecular Biology, Ghent University, Belgium |
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Abstract: | Immunogenic profile of certain cancer cell death mechanisms has been transmuted by research published over a period of last few years and this change has been so drastic that a new (sub)class of apoptotic cancer cell death, redefined as ‘immunogenic apoptosis’ has started taking shape. In fact, it has been shown that this chemotherapeutic agent-specific immunogenic cancer cell death modality has the capabilities to induce ‘anticancer vaccine effect’, in vivo. These new trends have given an opportunity to combine tumour cell kill and antitumour immunity within a single paradigm, a sort of ‘holy grail’ of anticancer therapeutics. At the molecular level, it has been shown that the immunological silhouette of these cell death pathways is defined by a set of molecules called ‘damage-associated molecular patterns (DAMPs)’. Various intracellular molecules like calreticulin (CRT), heat-shock proteins (HSPs), high-mobility group box-1 (HMGB1) protein, have been shown to be DAMPs exposed/secreted in a stress agent/factor-and cell death-specific manner. These discoveries have motivated further research into discovery of new DAMPs, new pathways for their exposure/secretion, search for new agents capable of inducing immunogenic cell death and urge to solve currently present problems with this paradigm. We anticipate that this emerging amalgamation of DAMPs, immunogenic cell death and anticancer therapeutics may be the key towards squelching cancer-related mortalities, in near future. |
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Keywords: | APCs, Antigen-presenting Cells ATP, Adenosine Triphosphate CD, Cluster of Differentiation CRT, Calreticulin DAMP, Damage-associated Molecular Patterns DC/DCs, Dendritic cell(s) DT-EGF, Epidermal Growth Factor Receptor-targeted Diphtheria Toxin eIF2α, Eukaryotic Initiation Factor 2α ER, Endoplasmic Reticulum HMGB1, High-Mobility Group Box-1 HSP, Heat Shock Protein(s) IFN, Interferon IL, Interleukin LPS, Lipopolysaccharide MAPK, Mitogen-activated Protein Kinase MHC, Major Histocompatibility Complex NFκB, Nuclear Factor kappa-light-chain-enhancer of activated B cells NK cells, Natural Killer Cells PAMP, Pathogen-associated Molecular Patterns PDT, Photodynamic Therapy PERK, PKR-like ER kinase PKR, Protein kinase R PS, Phosphatidylserine ROS, Reactive Oxygen Species TAA, Tumour-associated Antigen(s) TGF, Transforming Growth Factor TLR, Toll-like Receptor(s) TNF, Tumour Necrosis Factor UPR, Unfolded Protein Response UV, Ultra-violet (rays) |
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