title: The inhibition of TNF-alpha anti-tumoral properties by blocking antibodies promotes tumor growth in a rat model.
abstract: Tumor necrosis factor (TNF) antagonists represent a milestone in the therapy of autoimmune conditions. Anti-TNF antibodies have been approved for clinical use and during the last eight years thousands of patients have been treated. However, the long-term sequelae of anti-TNF agents in promoting carcinogenesis remain unclear. This study sought to define the role of intra-tumor TNF-alpha production on cancer cell progression and to determine whether TNF-alpha antibodies can suppress anti-tumoral immunity. Using an experimental animal tumor model we demonstrate that anti-TNF-alpha antibodies hinder anti-tumor immune responses and promote growth of immunogenic rat colon tumors (REG) that are always rejected by immunocompetent untreated rats. The major role of TNF-alpha in the anti-tumoral immune response was confirmed by transfecting progressive and tolerogenic rat colon tumor cells (PRO) with the TNF-alpha gene. PRO tumor cells secreting TNF-alpha induce tumor-infiltrating dendritic cell (DC) activation. This triggers a potent immune response leading to tumor rejection and long-lasting immunity. Therefore, the prominent role of TNF-alpha in anti-tumoral immune responses underscores the need for caution and close surveillance following the administration of TNF inhibitors.
authors.affiliation: INSERM U517, IFR 100, Faculty of Medicine, Dijon, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Larmonier
authors.forename: Dominique
authors.initials: D
authors.lastname: Cathelin
authors.forename: Claire
authors.initials: C
authors.lastname: Larmonier
authors.forename: Alexandra
authors.initials: A
authors.lastname: Nicolas
authors.forename: Delphine
authors.initials: D
authors.lastname: Merino
authors.forename: Nona
authors.initials: N
authors.lastname: Janikashvili
authors.forename: Sylvain
authors.initials: S
authors.lastname: Audia
authors.forename: Andrew
authors.initials: A
authors.lastname: Bateman
authors.forename: Jill
authors.initials: J
authors.lastname: Thompson
authors.forename: Tim
authors.initials: T
authors.lastname: Kottke
authors.forename: Thomas
authors.initials: T
authors.lastname: Hartung
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Katsanis
authors.forename: Richard
authors.initials: R
authors.lastname: Vile
authors.forename: Bernard
authors.initials: B
authors.lastname: Bonnotte
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000009:adverse effects* / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D007108:Immune Tolerance; D009389:Neovascularization, Pathologic / Q000276:immunology; D051381:Rats; D011923:Rats, Nude; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D019138:Antibodies, Blocking; D014409:Tumor Necrosis Factor-alpha