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

Details

Serval ID
serval:BIB_15F9FF107E5B
Type
Article: article from journal or magazin.
Collection
Publications
Title
Caspase-dependent immunogenicity of doxorubicin-induced tumor cell death.
Journal
The Journal of experimental medicine
Author(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
Publication state
Published
Issued date
19/12/2005
Peer-reviewed
Oui
Volume
202
Number
12
Pages
1691-1701
Language
english
Notes
Publication types: Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
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.

Keywords
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
Yes
Create date
13/09/2017 17:40
Last modification date
20/08/2019 12:45
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