Abstract
Natural killer (NK) cells and interferon- (IFN) gamma 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-gamma-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-gamma-deficient mice. These results suggested a substantial role of TRAIL as the effector molecule that eliminates subcutaneously developing TRAIL-sensitive tumors.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Monoclonal / immunology
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Antibodies, Monoclonal / pharmacology
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Apoptosis Regulatory Proteins
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Carcinoma, Renal Cell / immunology
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Carcinoma, Renal Cell / pathology
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Cytotoxicity, Immunologic
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Fibrosarcoma / immunology
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Fibrosarcoma / pathology
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Immunity, Innate
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Immunologic Surveillance / immunology*
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Injections, Subcutaneous
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Interferon-gamma / deficiency
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Interferon-gamma / genetics
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Interferon-gamma / physiology*
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Kidney Neoplasms / immunology
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Kidney Neoplasms / pathology
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Killer Cells, Natural / immunology*
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L Cells / immunology
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L Cells / transplantation
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Male
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Mast-Cell Sarcoma / immunology
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Mast-Cell Sarcoma / pathology
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Melanoma, Experimental / immunology
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Melanoma, Experimental / pathology
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Membrane Glycoproteins / antagonists & inhibitors
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Membrane Glycoproteins / deficiency
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / immunology
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Membrane Glycoproteins / physiology*
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C3H
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, SCID
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Neoplasm Transplantation
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Neoplasms, Experimental / immunology*
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Neoplasms, Experimental / pathology
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Perforin
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Pore Forming Cytotoxic Proteins
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TNF-Related Apoptosis-Inducing Ligand
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Tumor Cells, Cultured / immunology
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Tumor Cells, Cultured / transplantation
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Tumor Necrosis Factor-alpha / antagonists & inhibitors
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Tumor Necrosis Factor-alpha / immunology
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Tumor Necrosis Factor-alpha / physiology*
Substances
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Antibodies, Monoclonal
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Apoptosis Regulatory Proteins
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Membrane Glycoproteins
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Pore Forming Cytotoxic Proteins
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TNF-Related Apoptosis-Inducing Ligand
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Tnfsf10 protein, mouse
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Tumor Necrosis Factor-alpha
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Perforin
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Interferon-gamma