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Recently, much progress has been made in the field of tumor immunology. Much of this work has focused on understanding and exploiting the innate immune response to tumor cells. A novel human receptor-ligand system that mediates natural killer (NK) and γδ T-cell killing of carcinoma cells has been identified, and the functions of an equivalent system in mice are beginning to be explored. The mechanisms of action of an innate tumoricidal cytokine, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and of tumor cell resistance to it, are emerging, as are the ways in which tumor cells evade the damaging effects of IFN-γ and of complement. Overcoming tumor cell resistance to innate immune attack could prove to be a fruitful approach to cancer immunotherapy in the clinic.