Tumor Necrosis Factor:A Potent Mediator of Macrophage-Dependent Tumor-Cell Killing

Abstract

Macrophages (Mφ) 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 Mφ (aMφ) 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 Mφ in vitro [22]. Variants of these tumors demonstrating progressive growth in the normal host were found to invariably express an increased resistance to aMφ [22]. Furthermore, exposure of regressor tumor cells to aMφ in vitro also resulted in selection for Mφ-resistant cancer cells which displayed an increased early growth potential in vivo [22]. More recently we have utilized these tumor variants resistant to aMφ to explore the mechanism by which aMφ induce tumor cell destruction [23].