Immunogenic cell death, DAMPs and anticancer therapeutics: An emerging amalgamation

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 h...

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Bibliographic Details
Published in:Biochimica et biophysica acta 2010, Vol.1805 (1), p.53-71
Main Authors: Garg, Abhishek D., Nowis, Dominika, Golab, Jakub, Vandenabeele, Peter, Krysko, Dmitri V., Agostinis, Patrizia
Format: Article
Language:English
Subjects:
Anticancer therapeutics
Antineoplastic Agents - therapeutic use
Apoptosis - drug effects
Apoptosis - immunology
Autophagic cell death
Calreticulin
Cancer
DAMPs
Dendritic Cells
Heat-Shock Proteins - immunology
Humans
Immunogenic apoptosis
Lymphocyte Activation
Necrosis
Neoplasms - immunology
Neoplasms - pathology
T-Lymphocytes - immunology
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Summary: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.
ISSN:0304-419X
0006-3002
1879-2561
DOI:10.1016/j.bbcan.2009.08.003