Journal of Clinical Oncology, An American Society of Clinical Oncology Journal

Abstract Background: Tumor necrosis factor-alpha (TNFα) is a pleiotropic cytokine, with known antitumor activity, produced mainly by activated immune cells. Cancer cells neutralize TNFα by shedding soluble TNF receptors 1&2 (sTNFRs), which act asTNFα-binding decoys. In addition, sTNFRs can directly promote proliferation, survival, and chemoresistance of cancer cells by binding to membrane-bound TNFαand initiating retrograde signaling. Therefore, the reduction of systemic and intratumoral concentrations of sTNFRs represents a novel and unique strategy to reinvent the anticancer use of TNFα.