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

Thomas S. Griffith, Steven R. Wiley, Marek Z. Kubin, Lisa M. Sedger, Charles R. Maliszewski, Neil A. Fanger

Research output: Contribution to journalArticlepeer-review

387 Scopus citations

Abstract

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)-γ or -α and acquire the ability to kill tumor cells. Monocyte-mediated tumor cell apoptosis was TRAIL specific, as it could be inhibited with soluble TRAIL receptor. Moreover, IFN stimulation caused a concomitant loss of TRAIL receptor 2 expression, which coincides with monocyte acquisition of resistance to TRAIL-mediated apoptosis. These results define a novel mechanism of monocyte-induced cell cytotoxicity that requires TRAIL, and suggest that TRAIL is a key effector molecule in antitumor activity in vivo.

Original languageEnglish (US)
Pages (from-to)1343-1353
Number of pages11
JournalJournal of Experimental Medicine
Volume189
Issue number8
DOIs
StatePublished - Apr 19 1999

Keywords

  • Apoptosis
  • Human
  • Monocyte
  • TRAIL
  • Tumor

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