Afficher la couverture 'Calreticulin exposure dictates the immunogenicity of cancer cell death. | Obeid, Michel' en grand format
/5

0 avis

Calreticulin exposure dictates the immunogenicity of cancer cell death.

Archive ouverte

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

Edité par CCSD ; Nature Publishing Group -

International audience. 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.

Consulter en ligne

Suggestions

Du même auteur

Caspase-dependent immunogenicity of doxorubicin-induced tumor cell death

Archive ouverte | Casares, Noelia | CCSD

International audience. Systemic anticancer chemotherapy is immunosuppressive and mostly induces nonimmunogenic tumor cell death. Here, we show that even in the absence of any adjuvant, tumor cells dying in response...

Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy.

Archive ouverte | Apetoh, Lionel | CCSD

Conventional cancer treatments rely on radiotherapy and chemotherapy. Such treatments supposedly mediate their effects via the direct elimination of tumor cells. Here we show that the success of some protocols for anticancer thera...

Activation of the NLRP3 inflammasome in dendritic cells induces IL-1beta-dependent adaptive immunity against tumors.

Archive ouverte | Ghiringhelli, François | CCSD

International audience. The therapeutic efficacy of anticancer chemotherapies may depend on dendritic cells (DCs), which present antigens from dying cancer cells to prime tumor-specific interferon-gamma (IFN-gamma)-...

Chargement des enrichissements...