Monocyte-mediated tumoricidal activity via the tumor necrosis factor-related cytokine, TRAIL

TRAIL (tumor necrosis factor [TNF]-related apoptosis-inducing Ligand) is a molecule that displays potent antitumor activity against selected targets. The results presented here demonstrate that human monocytes rapidly express TRAIL, but not Fas ligand or TNF, after activation with interferon (IFN)-g amma or -alpha and acquire the ability to kill tumor cells. Monocyte-mediat ed tumor cell apoptosis was TRAIL specific, as it could be inhibited with s oluble TRAIL receptor. Moreover, IFN stimulation caused a concomitant loss of TRAIL receptor 2 expression, which coincides with monocyte acquisition o f resistance to TRAIL-mediated apoptosis. These results define a novel mech anism of monocyte-induced cell cytotoxicity that requires TRAIL, and sugges t that TRAIL is a key effector molecule in antitumor activity in vivo.