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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Institution: | 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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