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.
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19 April 1999
Article|
April 19 1999
Monocyte-mediated Tumoricidal Activity via the Tumor Necrosis Factor–related Cytokine, TRAIL
Thomas S. Griffith,
Thomas S. Griffith
From the *Department of Immunobiology, the ‡Department of Bioinformatics, and the §Department of Discovery Research, Immunex Corporation, Seattle, Washington 98101
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Steven R. Wiley,
Steven R. Wiley
From the *Department of Immunobiology, the ‡Department of Bioinformatics, and the §Department of Discovery Research, Immunex Corporation, Seattle, Washington 98101
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Marek Z. Kubin,
Marek Z. Kubin
From the *Department of Immunobiology, the ‡Department of Bioinformatics, and the §Department of Discovery Research, Immunex Corporation, Seattle, Washington 98101
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Lisa M. Sedger,
Lisa M. Sedger
From the *Department of Immunobiology, the ‡Department of Bioinformatics, and the §Department of Discovery Research, Immunex Corporation, Seattle, Washington 98101
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Charles R. Maliszewski,
Charles R. Maliszewski
From the *Department of Immunobiology, the ‡Department of Bioinformatics, and the §Department of Discovery Research, Immunex Corporation, Seattle, Washington 98101
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Neil A. Fanger
Neil A. Fanger
From the *Department of Immunobiology, the ‡Department of Bioinformatics, and the §Department of Discovery Research, Immunex Corporation, Seattle, Washington 98101
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Thomas S. Griffith
From the *Department of Immunobiology, the ‡Department of Bioinformatics, and the §Department of Discovery Research, Immunex Corporation, Seattle, Washington 98101
Steven R. Wiley
From the *Department of Immunobiology, the ‡Department of Bioinformatics, and the §Department of Discovery Research, Immunex Corporation, Seattle, Washington 98101
Marek Z. Kubin
From the *Department of Immunobiology, the ‡Department of Bioinformatics, and the §Department of Discovery Research, Immunex Corporation, Seattle, Washington 98101
Lisa M. Sedger
From the *Department of Immunobiology, the ‡Department of Bioinformatics, and the §Department of Discovery Research, Immunex Corporation, Seattle, Washington 98101
Charles R. Maliszewski
From the *Department of Immunobiology, the ‡Department of Bioinformatics, and the §Department of Discovery Research, Immunex Corporation, Seattle, Washington 98101
Neil A. Fanger
From the *Department of Immunobiology, the ‡Department of Bioinformatics, and the §Department of Discovery Research, Immunex Corporation, Seattle, Washington 98101
Address correspondence to Neil A. Fanger, Department of Discovery Research, Immunex Corporation, 51 University St., Seattle, WA 98101. E-mail: [email protected]
Received:
January 14 1999
Revision Received:
February 12 1999
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1999
J Exp Med (1999) 189 (8): 1343–1354.
Article history
Received:
January 14 1999
Revision Received:
February 12 1999
Citation
Thomas S. Griffith, Steven R. Wiley, Marek Z. Kubin, Lisa M. Sedger, Charles R. Maliszewski, Neil A. Fanger; Monocyte-mediated Tumoricidal Activity via the Tumor Necrosis Factor–related Cytokine, TRAIL . J Exp Med 19 April 1999; 189 (8): 1343–1354. doi: https://doi.org/10.1084/jem.189.8.1343
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