Involvement of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand in NK Cell-Mediated and IFN-γ-Dependent Suppression of Subcutaneous Tumor Growth

Natural killer (NK) cells and interferon- (IFN) γ have been implicated in immune surveillance against tumor development. Here we show tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which is a type II membrane protein belonging to the TNF family and plays a critical role in the NK cell-mediated and IFN-γ-dependent suppression of subcutaneous growth of TRAIL-sensitive tumors. Administration of a neutralizing monoclonal antibody against TRAIL promoted outgrowth of subcutaneously inoculated TRAIL-sensitive tumors (L929, LB27.4, and Renca) but not TRAIL-resistant tumors (P815 and B16). Such a protective effect of TRAIL against TRAIL-sensitive tumors was abrogated in NK cell-depleted or IFN-γ-deficient mice. These results suggested a substantial role of TRAIL as the effector molecule that eliminates subcutaneously developing TRAIL-sensitive tumors.