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Article Dans Une Revue Nature Medicine Année : 2007

Calreticulin exposure dictates the immunogenicity of cancer cell death.

Jean-Luc Perfettini
Guido Kroemer

Résumé

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.

Domaines

Immunologie
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Dates et versions

inserm-00451702 , version 1 (29-01-2010)

Identifiants

Citer

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