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

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

Research output: Contribution to journalArticle

28 Scopus citations

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-α production on cancer cell progression and to determine whether TNF-α antibodies can suppress anti-tumoral immunity. Using an experimental animal tumor model we demonstrate that anti-TNF-α 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-α in the anti-tumoral immune response was confirmed by transfecting progressive and tolerogenic rat colon tumor cells (PRO) with the TNF-α gene. PRO tumor cells secreting TNF-α 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-α in anti-tumoral immune responses underscores the need for caution and close surveillance following the administration of TNF inhibitors.

Original languageEnglish (US)
Pages (from-to)2345-2355
Number of pages11
JournalExperimental Cell Research
Volume313
Issue number11
DOIs
StatePublished - Jul 1 2007

Keywords

  • Dendritic cells
  • Gene expression
  • TNF-α
  • Tumor immunity

ASJC Scopus subject areas

  • Cell Biology

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  • Cite this

    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. (2007). The inhibition of TNF-α anti-tumoral properties by blocking antibodies promotes tumor growth in a rat model. Experimental Cell Research, 313(11), 2345-2355. https://doi.org/10.1016/j.yexcr.2007.03.027