Caspase-dependent immunogenicity of doxorubicin-induced tumor cell death.

Détails

ID Serval
serval:BIB_15F9FF107E5B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Caspase-dependent immunogenicity of doxorubicin-induced tumor cell death.
Périodique
The Journal of experimental medicine
Auteur⸱e⸱s
Casares N., Pequignot M.O., Tesniere A., Ghiringhelli F., Roux S., Chaput N., Schmitt E., Hamai A., Hervas-Stubbs S., Obeid M., Coutant F., Métivier D., Pichard E., Aucouturier P., Pierron G., Garrido C., Zitvogel L., Kroemer G.
ISSN
0022-1007 (Print)
ISSN-L
0022-1007
Statut éditorial
Publié
Date de publication
19/12/2005
Peer-reviewed
Oui
Volume
202
Numéro
12
Pages
1691-1701
Langue
anglais
Notes
Publication types: Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
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 to anthracyclins can elicit an effective antitumor immune response that suppresses the growth of inoculated tumors or leads to the regression of established neoplasia. Although both antracyclins and mitomycin C induced apoptosis with caspase activation, only anthracyclin-induced immunogenic cell death was immunogenic. Caspase inhibition by Z-VAD-fmk or transfection with the baculovirus inhibitor p35 did not inhibit doxorubicin (DX)-induced cell death, yet suppressed the immunogenicity of dying tumor cells in several rodent models of neoplasia. Depletion of dendritic cells (DCs) or CD8+T cells abolished the immune response against DX-treated apoptotic tumor cells in vivo. Caspase inhibition suppressed the capacity of DX-killed cells to be phagocytosed by DCs, yet had no effect on their capacity to elicit DC maturation. Freshly excised tumors became immunogenic upon DX treatment in vitro, and intratumoral inoculation of DX could trigger the regression of established tumors in immunocompetent mice. These results delineate a procedure for the generation of cancer vaccines and the stimulation of anti-neoplastic immune responses in vivo.

Mots-clé
Amino Acid Chloromethyl Ketones/pharmacology, Animals, Antibiotics, Antineoplastic/pharmacology, Antibiotics, Antineoplastic/therapeutic use, Apoptosis/drug effects, CD8-Positive T-Lymphocytes/immunology, Caspase Inhibitors, Caspases/metabolism, Cell Line, Tumor, Dendritic Cells/immunology, Doxorubicin/pharmacology, Doxorubicin/therapeutic use, Immunoblotting, In Situ Nick-End Labeling, Mice, Mitomycin/pharmacology, Mitomycin/therapeutic use, Neoplasms/drug therapy, Neoplasms/immunology, Neoplasms/prevention & control, Rats, Vaccination/methods, Viral Proteins/genetics, Viral Proteins/pharmacology
Pubmed
Web of science
Open Access
Oui
Création de la notice
13/09/2017 17:40
Dernière modification de la notice
20/08/2019 12:45
Données d'usage