Calreticulin exposure dictates the immunogenicity of cancer cell death.

Details

Serval ID
serval:BIB_BDFD105248D4
Type
Article: article from journal or magazin.
Collection
Publications
Title
Calreticulin exposure dictates the immunogenicity of cancer cell death.
Journal
Nature medicine
Author(s)
Obeid M., Tesniere A., Ghiringhelli F., Fimia G.M., Apetoh L., Perfettini J.L., Castedo M., Mignot G., Panaretakis T., Casares N., Métivier D., Larochette N., van Endert P., Ciccosanti F., Piacentini M., Zitvogel L., Kroemer G.
ISSN
1078-8956 (Print)
ISSN-L
1078-8956
Publication state
Published
Issued date
01/2007
Peer-reviewed
Oui
Volume
13
Number
1
Pages
54-61
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Anthracyclin-treated tumor cells are particularly effective in eliciting an anticancer immune response, whereas other DNA-damaging agents such as etoposide and mitomycin C do not induce immunogenic cell death. Here we show that anthracyclins induce the rapid, preapoptotic translocation of calreticulin (CRT) to the cell surface. Blockade or knockdown of CRT suppressed the phagocytosis of anthracyclin-treated tumor cells by dendritic cells and abolished their immunogenicity in mice. The anthracyclin-induced CRT translocation was mimicked by inhibition of the protein phosphatase 1/GADD34 complex. Administration of recombinant CRT or inhibitors of protein phosphatase 1/GADD34 restored the immunogenicity of cell death elicited by etoposide and mitomycin C, and enhanced their antitumor effects in vivo. These data identify CRT as a key feature determining anticancer immune responses and delineate a possible strategy for immunogenic chemotherapy.

Keywords
Animals, Anthracyclines/pharmacology, Anthracyclines/therapeutic use, Antigens, Differentiation/metabolism, Antineoplastic Agents/pharmacology, Antineoplastic Agents/therapeutic use, Apoptosis/drug effects, Apoptosis/immunology, Calreticulin/genetics, Calreticulin/immunology, Calreticulin/metabolism, Cell Cycle Proteins/antagonists & inhibitors, Cell Cycle Proteins/metabolism, Cell Line, Tumor, Cell Membrane/drug effects, Cell Membrane/immunology, Cell Membrane/metabolism, Colonic Neoplasms/drug therapy, Colonic Neoplasms/metabolism, Colonic Neoplasms/pathology, Dendritic Cells/immunology, Electrophoresis, Gel, Two-Dimensional, Etoposide/pharmacology, Etoposide/therapeutic use, Immunoblotting, Mice, Mice, Inbred BALB C, Mice, Nude, Mitomycin/pharmacology, Mitomycin/therapeutic use, Neoplasms, Experimental/drug therapy, Neoplasms, Experimental/immunology, Neoplasms, Experimental/metabolism, Phagocytosis/immunology, Protein Phosphatase 1, Protein Transport/drug effects, RNA Interference, Recombinant Proteins/pharmacology
Pubmed
Web of science
Create date
13/09/2017 17:39
Last modification date
20/08/2019 15:32
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