Molecular determinants of immunogenic cell death: surface exposure of calreticulin makes the difference.

Details

Serval ID
serval:BIB_1ABCF83EC0BD
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Title
Molecular determinants of immunogenic cell death: surface exposure of calreticulin makes the difference.
Journal
Journal of molecular medicine
Author(s)
Chaput N., De Botton S., Obeid M., Apetoh L., Ghiringhelli F., Panaretakis T., Flament C., Zitvogel L., Kroemer G.
ISSN
0946-2716 (Print)
ISSN-L
0946-2716
Publication state
Published
Issued date
10/2007
Peer-reviewed
Oui
Volume
85
Number
10
Pages
1069-1076
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Review
Publication Status: ppublish
Abstract
The treatment of cancer by chemotherapy causes tumour cell death, mostly by apoptosis. This tumour cell death may or may not elicit an immune response. At least in some cases, the efficacy of chemotherapy critically depends on the induction of immunogenic cell death that is a type of cell demise that stimulates the activation of an adaptative anti-tumour immune response, which in turn helps to eradicate residual cancer (stem) cells. Indeed, anthracyclins care more efficient in curing tumours in immunocompetent than in T cell-deficient mice. The molecular mechanism implicated in this anti-tumour T cell activation was recently discovered. Anthracyclins cause immunogenic cell death due to their specific capacity to stimulate the translocation of calreticulin to the cell surface. Calreticulin then acts as an "eat me" signal for dendritic cells, allowing them to phagocytose tumour cells and to prime tumour antigen-specific cytotoxic T cells. Importantly, non-immunogenic chemotherapy can be rendered immunogenic by adsorbing recombinant calreticulin to tumour cells or by enforcing the translocation of endogenous calreticulin to the cell surface by means of PP1/GADD34 inhibitors. This strategy could have major implications for the treatment of human cancer. Indeed, in vivo treatments with anthracyclins can cause the translocation of calreticulin to the surface of circulating tumour cells, in patients with acute myeloid leukaemia (AML). The challenge will be to determine whether the exposure of calreticulin translocation on the tumour cell surface is linked to chemotherapy-induced anti-tumour immune responses and therapeutic efficacy in human cancer.

Keywords
Animals, Anthracyclines/pharmacology, Anthracyclines/therapeutic use, Antigens, Neoplasm/drug effects, Antigens, Neoplasm/immunology, Antigens, Neoplasm/metabolism, Antigens, Surface/drug effects, Antigens, Surface/immunology, Antigens, Surface/metabolism, Antineoplastic Agents/pharmacology, Apoptosis/drug effects, Apoptosis/immunology, Calreticulin/immunology, Calreticulin/metabolism, Cell Line, Tumor, Cell Membrane/drug effects, Cell Membrane/immunology, Cell Membrane/metabolism, Dendritic Cells/immunology, Humans, Mice, Models, Biological, Neoplasms, Experimental/immunology, T-Lymphocytes, Cytotoxic/immunology
Pubmed
Web of science
Create date
13/09/2017 17:34
Last modification date
20/08/2019 12:51
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