title: Apoptotic, necrotic, or fused tumor cells: an equivalent source of antigen for dendritic cell loading.
abstract: 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.
authors.affiliation: INSERM U517, IFR 100, Faculty of Medicine and Pharmacy, 7 Boulevard Jeanne d'Arc, 21079 Dijon, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Larmonier
authors.forename: Delphine
authors.initials: D
authors.lastname: Mérino
authors.forename: Alexandra
authors.initials: A
authors.lastname: Nicolas
authors.forename: Dominique
authors.initials: D
authors.lastname: Cathelin
authors.forename: Angélique
authors.initials: A
authors.lastname: Besson
authors.forename: Andrew
authors.initials: A
authors.lastname: Bateman
authors.forename: Eric
authors.initials: E
authors.lastname: Solary
authors.forename: François
authors.initials: F
authors.lastname: Martin
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Katsanis
authors.forename: Bernard
authors.initials: B
authors.lastname: Bonnotte
mesh_terms: 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
chemical_list: D016328:NF-kappa B; D050794:STAT1 Transcription Factor; D018664:Interleukin-12