The inhibition of TNF-alpha anti-tumoral properties by blocking antibodies promotes tumor growth in a rat model.
Fiche publication
Date publication
juillet 2007
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BONNOTTE Bernard
Tous les auteurs :
Larmonier N, Cathelin D, Larmonier C, Nicolas A, Merino D, Janikashvili N, Audia S, Bateman A, Thompson J, Kottke T, Hartung T, Katsanis E, Vile R, Bonnotte B
Lien Pubmed
Résumé
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.
Référence
Exp Cell Res. 2007 Jul 1;313(11):2345-55