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Front Immunol. 2015 Nov 20;6:588. doi: 10.3389/fimmu.2015.00588. eCollection 2015.

Molecular and Translational Classifications of DAMPs in Immunogenic Cell Death.

Author information

1
Cell Death Research and Therapy Laboratory, Department of Cellular Molecular Medicine, KU Leuven - University of Leuven , Leuven , Belgium.
2
Equipe 11 Labellisée Ligue Contre le Cancer, Centre de Recherche des Cordeliers , Paris , France ; U1138, INSERM , Paris , France ; Université Paris Descartes, Sorbonne Paris Cité , Paris , France ; Université Pierre et Marie Curie , Paris , France ; Gustave Roussy Comprehensive Cancer Institute , Villejuif , France.
3
U866, INSERM , Dijon , France ; Faculté de Médecine, Université de Bourgogne , Dijon , France ; Centre Georges François Leclerc , Dijon , France.
4
Department of Gynaecology and Obstetrics, UZ Leuven , Leuven , Belgium ; Laboratory of Gynaecologic Oncology, Department of Oncology, Leuven Cancer Institute, KU Leuven , Leuven , Belgium.
5
Department of Microbiology, Biochemistry, and Molecular Genetics, University Hospital Cancer Center, Rutgers Cancer Institute of New Jersey, New Jersey Medical School , Newark, NJ , USA.
6
Laboratory of Molecular and Cellular Therapy, Vrije Universiteit Brussel , Jette , Belgium.
7
Faculty of Life Sciences, University of Manchester , Manchester , UK.
8
Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nurnberg , Erlangen , Germany.
9
Department of Experimental Medicine, Sapienza University of Rome , Rome , Italy.
10
de Duve Institute, Université Catholique de Louvain , Brussels , Belgium.
11
Department of Radiation Oncology, University Hospitals Leuven, KU Leuven - University of Leuven , Leuven , Belgium.
12
Department of Biological and Environmental Science and Technology, University of Salento , Salento , Italy.
13
Laboratory for Molecular Biodiscovery, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven - University of Leuven , Leuven , Belgium.
14
Sapienza University of Rome , Rome , Italy.
15
SOTIO , Prague , Czech Republic ; Department of Immunology, 2nd Faculty of Medicine, University Hospital Motol, Charles University , Prague , Czech Republic.
16
Department of Radiation Oncology, Universitätsklinikum Erlangen , Erlangen , Germany.
17
Department of Immunology, Medical University of Warsaw , Warsaw , Poland.
18
Biotherapy and Vaccine Unit, Institut Pasteur , Paris , France.
19
Wellman Center for Photomedicine, Massachusetts General Hospital , Boston, MA , USA.
20
Cancer Gene Therapy Group, Transplantation Laboratory, Haartman Institute, University of Helsinki , Helsinki , Finland ; Helsinki University Hospital Comprehensive Cancer Center , Helsinki , Finland ; TILT Biotherapeutics Ltd. , Helsinki , Finland.
21
Recombinant Vaccine Group, Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health , Bethesda, MD , USA.
22
Equipe 11 Labellisée Ligue Contre le Cancer, Centre de Recherche des Cordeliers , Paris , France ; U1138, INSERM , Paris , France ; Université Paris Descartes, Sorbonne Paris Cité , Paris , France ; Université Pierre et Marie Curie , Paris , France ; Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute , Villejuif , France.
23
Equipe 11 Labellisée Ligue Contre le Cancer, Centre de Recherche des Cordeliers , Paris , France ; U1138, INSERM , Paris , France ; Université Paris Descartes, Sorbonne Paris Cité , Paris , France ; Université Pierre et Marie Curie , Paris , France ; Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute , Villejuif , France ; Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP , Paris , France ; Department of Women's and Children's Health, Karolinska University Hospital , Stockholm , Sweden.
24
Molecular Signaling and Cell Death Unit, Inflammation Research Center, VIB , Ghent , Belgium ; Department of Biomedical Molecular Biology, Ghent University , Ghent , Belgium.
25
Molecular ImmunoRheumatology, INSERM UMRS1109, Laboratory of Excellence Transplantex, University of Strasbourg , Strasbourg , France.
26
Institute of Molecular Biosciences, NAWI Graz, University of Graz , Graz , Austria ; BioTechMed Graz , Graz , Austria.
27
IRRCS Istituto Scientifico San Raffaele, Università Vita-Salute San Raffaele , Milan , Italy.
28
Translational Research Institute, University of Queensland Diamantina Institute, University of Queensland , Wooloongabba, QLD , Australia.
29
Laboratory of Cellular and Molecular Nutrition, Department of Ecological and Biological Sciences, Tuscia University , Viterbo , Italy.
30
Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München , Munich , Germany.
31
Department of Medical Oncology, University Hospital , Bern , Switzerland.
32
INSERM, U1065, Université de Nice-Sophia-Antipolis, Centre Méditerranéen de Médecine Moléculaire (C3M), Équipe "Contrôle Métabolique des Morts Cellulaires" , Nice , France.
33
Department of Oncology, University of Turin , Turin , Italy.
34
Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Insitute , Herston, QLD , Australia ; School of Medicine, University of Queensland , Herston, QLD , Australia.
35
Department of Paediatric Haematology and Oncology, Children's Clinic, Jena University Hospital , Jena , Germany.
36
Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Institut du Cancer de Montréal, Faculté de Pharmacie, Université de Montréal , Montreal, QC , Canada.
37
Laboratory of Pediatric Immunology, Department of Microbiology and Immunology, KU Leuven - University of Leuven , Leuven , Belgium.
38
Ludwig Institute for Cancer Research, de Duve Institute, Université Catholique de Louvain , Brussels , Belgium.
39
Department of Ecological and Biological Sciences, Tuscia University , Viterbo , Italy.
40
Gustave Roussy Comprehensive Cancer Institute , Villejuif , France ; University of Paris Sud , Le Kremlin-Bicêtre , France ; U1015, INSERM , Villejuif , France ; Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 507 , Villejuif , France.

Abstract

The immunogenicity of malignant cells has recently been acknowledged as a critical determinant of efficacy in cancer therapy. Thus, besides developing direct immunostimulatory regimens, including dendritic cell-based vaccines, checkpoint-blocking therapies, and adoptive T-cell transfer, researchers have started to focus on the overall immunobiology of neoplastic cells. It is now clear that cancer cells can succumb to some anticancer therapies by undergoing a peculiar form of cell death that is characterized by an increased immunogenic potential, owing to the emission of the so-called "damage-associated molecular patterns" (DAMPs). The emission of DAMPs and other immunostimulatory factors by cells succumbing to immunogenic cell death (ICD) favors the establishment of a productive interface with the immune system. This results in the elicitation of tumor-targeting immune responses associated with the elimination of residual, treatment-resistant cancer cells, as well as with the establishment of immunological memory. Although ICD has been characterized with increased precision since its discovery, several questions remain to be addressed. Here, we summarize and tabulate the main molecular, immunological, preclinical, and clinical aspects of ICD, in an attempt to capture the essence of this phenomenon, and identify future challenges for this rapidly expanding field of investigation.

KEYWORDS:

anti-tumor immunity; immunogenicity; immunotherapy; molecular medicine; oncoimmunology; patient prognosis; translational medicine

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