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Front Immunol. 2015 Apr 24;6:187. doi: 10.3389/fimmu.2015.00187. eCollection 2015.

Combinatorial strategies for the induction of immunogenic cell death.

Author information

1
Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers , Paris , France ; U1138, INSERM , Paris , France ; Metabolomics and Cell Biology Platforms, Gustave Roussy Campus Cancer , Villejuif , France ; Faculté de Medecine, Université Paris-Sud , Le Kremlin-Bicêtre , France.
2
Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers , Paris , France ; U1138, INSERM , Paris , France ; Metabolomics and Cell Biology Platforms, Gustave Roussy Campus Cancer , Villejuif , France ; Department of Chemistry, University of Coimbra , Coimbra , Portugal.
3
Laboratory for General Biochemistry and Physical Pharmacy, Faculty of Pharmacy, Ghent University , Ghent , Belgium ; Laboratory of Molecular and Cellular Therapy, Vrije Universiteit Brussel , Jette , Belgium.
4
Laboratory of Molecular and Cellular Therapy, Vrije Universiteit Brussel , Jette , Belgium.
5
Sotio a.c. , Prague , Czech Republic ; Department of Immunology, 2nd Faculty of Medicine, University Hospital Motol, Charles University , Prague , Czech Republic.
6
Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers , Paris , France ; U1138, INSERM , Paris , France ; Gustave Roussy Campus Cancer , Villejuif , France ; Université Paris Descartes , Paris , France ; Université Pierre et Marie Curie , Paris , France.
7
Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers , Paris , France ; U1138, INSERM , Paris , France ; Metabolomics and Cell Biology Platforms, Gustave Roussy Campus Cancer , Villejuif , France.
8
Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers , Paris , France ; U1138, INSERM , Paris , France ; Metabolomics and Cell Biology Platforms, Gustave Roussy Campus Cancer , Villejuif , France ; Department of Immunology, 2nd Faculty of Medicine, University Hospital Motol, Charles University , Prague , Czech Republic ; Université Paris Descartes , Paris , France ; Université Pierre et Marie Curie , Paris , France ; Pôle de Biologie, Hopitâl Européen George Pompidou, AP-HP , Paris , France.

Abstract

The term "immunogenic cell death" (ICD) is commonly employed to indicate a peculiar instance of regulated cell death (RCD) that engages the adaptive arm of the immune system. The inoculation of cancer cells undergoing ICD into immunocompetent animals elicits a specific immune response associated with the establishment of immunological memory. Only a few agents are intrinsically endowed with the ability to trigger ICD. These include a few chemotherapeutics that are routinely employed in the clinic, like doxorubicin, mitoxantrone, oxaliplatin, and cyclophosphamide, as well as some agents that have not yet been approved for use in humans. Accumulating clinical data indicate that the activation of adaptive immune responses against dying cancer cells is associated with improved disease outcome in patients affected by various neoplasms. Thus, novel therapeutic regimens that trigger ICD are urgently awaited. Here, we discuss current combinatorial approaches to convert otherwise non-immunogenic instances of RCD into bona fide ICD.

KEYWORDS:

ATP; HMGB1; autophagy; calreticulin; endoplasmic reticulum stress; type I interferon

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