Apoptotic, necrotic, or fused tumor cells: an equivalent source of antigen for dendritic cell loading

The identification of the most efficient strategy for tumor antigen loading of dendritic cells (DCs) remains a challenge in cancer immunotherapy protocols. Autologous dead tumor cells have been demonstrated to constitute an acceptable source of multiple tumor-associated antigens (TAA) to pulse DCs....

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Published inApoptosis (London) Vol. 11; no. 9; pp. 1513 - 1524
Main Authors Larmonier, Nicolas, Mérino, Delphine, Nicolas, Alexandra, Cathelin, Dominique, Besson, Angélique, Bateman, Andrew, Solary, Eric, Martin, François, Katsanis, Emmanuel, Bonnotte, Bernard
Format Journal Article
LanguageEnglish
Published Netherlands Springer Nature B.V 01.09.2006
Subjects
Animals
Antigen Presentation - immunology
Apoptosis
Apoptosis - immunology
Bone marrow
Cancer
Cell Fusion
Colonic Neoplasms - immunology
Dendritic Cells - immunology
Immunotherapy
Interleukin-12 - biosynthesis
Lymphocyte Activation
Mortality
Necrosis - immunology
NF-kappa B - metabolism
Phenotype
Proteins
Rats
STAT1 Transcription Factor - metabolism
T-Cell Antigen Receptor Specificity
Tumor Cells, Cultured
Tumors
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Summary:The identification of the most efficient strategy for tumor antigen loading of dendritic cells (DCs) remains a challenge in cancer immunotherapy protocols. Autologous dead tumor cells have been demonstrated to constitute an acceptable source of multiple tumor-associated antigens (TAA) to pulse DCs. However the optimal approach for inducing cell death that would lead to effective endocytosis and activation of DCs remains controversial. In this study we have induced and defined 3 distinct mechanisms of tumor cell death (apoptosis, necrosis and fusion-mediated cell death), and investigated their differential effects on DCs. Bone marrow-derived DCs demonstrated comparable uptake of primary apoptotic, necrotic, or fused dead tumor cells. Furthermore, the distinct modes of cancer cell death had analogous potential in activating the transcription factors NF-kappaB and STAT1 and in maturing DCs, resulting in an equally effective stimulation of immune T cells. The current study therefore provides further informations on the use of dead whole tumor cells as antigen sources for effective active anti-cancer immunotherapy.
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ISSN:1360-8185
1573-675X
DOI:10.1007/s10495-006-8765-0