Tumor necrosis factor: a potent mediator of macrophage-dependent tumor-cell killing.

Macrophages (Me/» can be activated to show highly selective cytotoxicity toward malignant cells in vitro [6, 8, 9, 13, 14] and there is some evidence that they may destroy neoplastic cells in vivo [1]. The importance of activated Me/> (aMe/» in controlling tumor growth in vivo has been further implicated in experiments involving murine ultraviolet light (UV)-induced tumors, which are highly immunogenic regressor tumors [10] sensitive to Me/> in vitro [22]. Variants of these tumors demonstrating progressive growth in the normal host were found to invariably express an increased resistance to aMe/> [22]. Furthermore, exposure of regressor tumor cells to aMe/> in vitro also resulted in selection for Me/>-resistant cancer cells which displayed an increased early growth potential in vivo [22]. More recently we have utilized these tumor variants resistant to aMe/> to explore the mechanism by which aMe/> induce tumor cell destruction [23]. Our results suggest a major role for tumor necrosis factor type ex (TNF-ex) in Me/>-mediated tumor cell killing in vitro and in vivo [23].