The inhibition of TNF-α anti-tumoral properties by blocking antibodies promotes tumor growth in a rat model Academic Article uri icon

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

  • Larmonier, Nicolas
  • Cathelin, Dominique
  • Larmonier, Claire
  • Nicolas, Alexandra
  • Merino, Delphine
  • Janikashvili, Nona
  • Audia, Sylvain
  • Bateman, Andrew
  • Thompson, Jill
  • Kottke, Tim
  • Hartung, Thomas
  • Katsanis, Emmanuel
  • Vile, Richard
  • Bonnotte, Bernard

publication date

  • July 2007