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Calreticulin exposure dictates the immunogenicity of cancer cell death.

Michel Obeid 1 Antoine Tesniere 1 François Ghiringhelli 2 Gian Maria Fimia 3 Lionel Apetoh 2 Jean-Luc Perfettini 1 Maria Castedo 1 Grégoire Mignot 2 Theoharis Panaretakis 1 Noelia Casares 1 Didier Métivier 1 Nathanael Larochette 1 Peter van Endert 4 Fabiola Ciccosanti 3 Mauro Piacentini 3, 5 Laurence Zitvogel 2 Guido Kroemer 1
1 U848 - Apoptose, cancer et immunité
2 Role des Cellules Dendritiques Dans la Regulation des Effecteurs de l'Immunite Antitumorale
3 National Institute for Infectious Diseases
4 Diabète de Type 1 : mécanismes et traitements immunologiques
5 Department of Biology
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.
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https://www.hal.inserm.fr/inserm-00451702
Contributor : Grégoire Mignot <>
Submitted on : Friday, January 29, 2010 - 5:37:02 PM
Last modification on : Wednesday, October 14, 2020 - 3:45:13 AM

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UNIV-PARIS5 | IGR | FNCLCC | USPC | UNIV-PARIS

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Michel Obeid, Antoine Tesniere, François Ghiringhelli, Gian Maria Fimia, Lionel Apetoh, et al.. Calreticulin exposure dictates the immunogenicity of cancer cell death.. Nature Medicine, Nature Publishing Group, 2007, 13 (1), pp.54-61. ⟨10.1038/nm1523⟩. ⟨inserm-00451702⟩

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