AACR Journal of Cancer Research Proceedings

Abstract Introduction: Tumor necrosis factor-alpha (TNFα) is a pleiotropic cytokine, with known antitumor activity, produced mainly by activated immune cells. Cancer cells can neutralize TNFα by shedding soluble TNF receptors 1&2 (sTNFRs), which act as TNFα-binding decoys. In addition, sTNFRs can directly promote proliferation, survival, and chemoresistance of cancer cells by binding to membrane-bound TNFα and initiating retrograde signaling. Therefore, the reduction of systemic and intratumoral concentrations of sTNFRs represents a novel and unique anticancer strategy, since systemic recombinant TNFα treatment strategies require very high doses to achieve antitumor activity, and are feasible only in an isolated limb perfusion setting.