Infliximab enhances the therapeutic effects of 5-fluorouracil resulting in tumor regression in colon cancer

Colon cancer (CC) is among the most common malignant diseases with a dismal survival. Tumor necrosis factor-alpha (TNF-alpha) has been identified as a therapeutic target in various cancers, and anti-TNF-alpha treatment has shown promising effects in different cancer models. However, if TNF-alpha can be targeted in CC, the therapeutic values of anti-TNF-alpha treatment in CC remain unknown. Our study indicated that TNF-alpha is highly expressed in CC cell lines and patient tumor samples. High expression of TNF-alpha is an independent adverse prognosticator of CC. Targeting the TNF-alpha by its antibody infliximab induced antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity and enhanced apoptosis leading to cell death. The combination of infliximab with 5-fluorouracil showed better responses in vitro and in vivo than 5-fluorouracil alone. In conclusion, this study identified TNF-alpha as a target of CC and anti-TNF-alpha treatment synergized with chemotherapy leading to a better outcome in preclinical models.