Calreticulin exposure dictates the immunogenicity of cancer cell death

Michel Obeid, Antoine Tesniere, François Ghiringhelli, Gian Maria Fimia, Lionel Apetoh, Jean Luc Perfettini, Maria Castedo, Grégoire Mignot, Theoharis Panaretakis, Noelia Casares, Didier Métivier, Nathanael Larochette, Peter Van Endert, Fabiola Ciccosanti, Mauro Piacentini, Laurence Zitvogel, Guido Kroemer

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)54-61
Number of pages8
JournalNature Medicine
Volume13
Issue number1
DOIs
Publication statusPublished - Jan 2007

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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  • Cite this

    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. (2007). Calreticulin exposure dictates the immunogenicity of cancer cell death. Nature Medicine, 13(1), 54-61. https://doi.org/10.1038/nm1523