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. 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.
Larmonier
Nicolas
N
INSERM U517, IFR 100, Faculty of Medicine and Pharmacy, 7 Boulevard Jeanne d'Arc, 21079 Dijon, France.
Mérino
Delphine
D
Nicolas
Alexandra
A
Cathelin
Dominique
D
Besson
Angélique
A
Bateman
Andrew
A
Solary
Eric
E
Martin
François
F
Katsanis
Emmanuel
E
Bonnotte
Bernard
B
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology*; D002459:Cell Fusion; D003110:Colonic Neoplasms / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D018664:Interleukin-12 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D016328:NF-kappa B / Q000378:metabolism; D009336:Necrosis / Q000276:immunology*; D010641:Phenotype; D051381:Rats; D050794:STAT1 Transcription Factor / Q000378:metabolism; D037182:T-Cell Antigen Receptor Specificity; D014407:Tumor Cells, Cultured
D016328:NF-kappa B; D050794:STAT1 Transcription Factor; D018664:Interleukin-12