Involvement of tumor necrosis factor-related apoptosis-inducing ligand in NK cell-mediated and IFN-gamma-dependent suppression of subcutaneous tumor growth.
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.
Takeda
K
K
Department of Immunology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, Japan. ktakeda@med.juntendo.ac.jp
Smyth
M J
MJ
Cretney
E
E
Hayakawa
Y
Y
Yamaguchi
N
N
Yagita
H
H
Okumura
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D051017:Apoptosis Regulatory Proteins; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000473:pathology; D003602:Cytotoxicity, Immunologic; D005354:Fibrosarcoma / Q000276:immunology / Q000473:pathology; D007113:Immunity, Innate; D007157:Immunologic Surveillance / Q000276:immunology*; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007680:Kidney Neoplasms / Q000276:immunology / Q000473:pathology; D007694:Killer Cells, Natural / Q000276:immunology*; D007739:L Cells / Q000276:immunology / Q000637:transplantation; D008297:Male; D012515:Mast-Cell Sarcoma / Q000276:immunology / Q000473:pathology; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; D014407:Tumor Cells, Cultured / Q000276:immunology / Q000637:transplantation; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505654:Tnfsf10 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D054353:Perforin; D007371:Interferon-gamma