Possible Mechanisms for Tumour Cell Sensitivity to TNF-a and Potential Therapeutic Applications

TNF is a macrophage / monocyte-derived cytokine with cytostatic and cytotoxic anti-tumour activity. TNF-alpha can cause haemorrhagic necrosis and regression of experimental tumours. Nevertheless, the TNF-alpha doses required to cure tumour-bearing mice lead to injury of normal tissues and, eventually, may cause a lethal shock syndrome. This toxicity implies severe limitations for the therapeutic use of TNF-a. Reactive oxygen intermediates (ROIs) are involved in TNF-a-induced cell killing. Different studies are consistent with the hypothesis that tumour cell sensitivity to TNF-alpha is related to its capacity to buffer oxidative attack. Recently, we have demonstrated that the sensitivity of …