Tumor Necrosis Factor and Cancer

Tumor necrosis factor a (TNF) is a potent, pleiotropic, proinflammatory cytokine that is produced by macrophages, neutrophils, fibroblasts, keratinocytes, NK, T-and B-cells and also by tumor cells. TNF binds to either of two receptors, TNF-R1 or TNF-R2, expressed on virtually all mammalian cell types. TNF was named because of its ability, when administered in pharmacologic doses, to cause necrosis of tumors in experimental models. Recombinant TNF is approved in Europe to be given locoregionally as a therapy for sarcoma. TNF produced by the body mediates host responses in acute and chronic inflammatory conditions and aids in host protection from infection and malignancy. The biology of the TNF/TNF-receptor system was reviewed by Palladino et al. 2003 (1).