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Cancer Immunology, Peter MacCallum Cancer Institute, St. Andrews Place, East Melbourne, Victoria, Australia;
Division of Molecular Immunology, Center of Biomedical Sciences, Chiba University School of Medicine, Chiba, Japan
IL-12 has been demonstrated to have potent anti-tumor activities in a variety of mouse tumor models, but the relative roles of NK, NKT, and T cells and their effector mechanisms in these responses have not been fully addressed. Using a spectrum of gene-targeted or Ab-treated mice we have shown that for any particular tumor model the effector mechanisms downstream of IL-12 often mimic the natural immune response to that tumor. For example, metastasis of the MHC class I-deficient lymphoma, EL4-S3, was strictly controlled by NK cells using perforin either naturally or following therapy with high-dose IL-12. Intriguingly, in B16F10 and RM-1 tumor models both NK and NKT cells contribute to natural protection from tumor metastasis. In these models, a lower dose of IL-12 or delayed administration of IL-12 dictated a greater relative role of NKT cells in immune protection from tumor metastasis. Overall, both NK and NKT cells can contribute to natural and IL-12-induced immunity against tumors, and the relative role of each population is tumor and therapy dependent.
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J. C. Baker-LePain, M. Sarzotti, T. A. Fields, C.-Y. Li, and C. V. Nicchitta GRP94 (gp96) and GRP94 N-Terminal Geldanamycin Binding Domain Elicit Tissue Nonrestricted Tumor Suppression J. Exp. Med., December 2, 2002; 196(11): 1447 - 1459. [Abstract] [Full Text] [PDF]
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Y. Hayakawa, K. Takeda, H. Yagita, M. J. Smyth, L. Van Kaer, K. Okumura, and I. Saiki IFN-gamma -mediated inhibition of tumor angiogenesis by natural killer T-cell ligand, alpha -galactosylceramide Blood, August 13, 2002; 100(5): 1728 - 1733. [Abstract] [Full Text] [PDF]
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N. Y. Crowe, M. J. Smyth, and D. I. Godfrey A Critical Role for Natural Killer T Cells in Immunosurveillance of Methylcholanthrene-induced Sarcomas J. Exp. Med., July 1, 2002; 196(1): 119 - 127. [Abstract] [Full Text] [PDF]
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S. E.A. Street, J. A. Trapani, D. MacGregor, and M. J. Smyth Suppression of Lymphoma and Epithelial Malignancies Effected by Interferon {gamma} J. Exp. Med., July 1, 2002; 196(1): 129 - 134. [Abstract] [Full Text] [PDF]
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J. M. Kelly, K. Takeda, P. K. Darcy, H. Yagita, and M. J. Smyth A Role for IFN-{gamma} in Primary and Secondary Immunity Generated by NK Cell-Sensitive Tumor-Expressing CD80 In Vivo J. Immunol., May 1, 2002; 168(9): 4472 - 4479. [Abstract] [Full Text] [PDF]
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M. J. Smyth, N. Y. Crowe, D. G. Pellicci, K. Kyparissoudis, J. M. Kelly, K. Takeda, H. Yagita, and D. I. Godfrey Sequential production of interferon-gamma by NK1.1+ T cells and natural killer cells is essential for the antimetastatic effect of alpha -galactosylceramide Blood, February 15, 2002; 99(4): 1259 - 1266. [Abstract] [Full Text] [PDF]
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T. A. Gruber, D. C. Skelton, and D. B. Kohn Requirement for NK Cells in CD40 Ligand-Mediated Rejection of Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Cells J. Immunol., January 1, 2002; 168(1): 73 - 80. [Abstract] [Full Text] [PDF]
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S. Muhammad Ali Tahir, O. Cheng, A. Shaulov, Y. Koezuka, G. J. Bubley, S. B. Wilson, S. P. Balk, and M. A. Exley Loss of IFN-{gamma} Production by Invariant NK T Cells in Advanced Cancer J. Immunol., October 1, 2001; 167(7): 4046 - 4050. [Abstract] [Full Text] [PDF]
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C. Karnbach, M. R. Daws, E. C. Niemi, and M. C. Nakamura Immune Rejection of a Large Sarcoma Following Cyclophosphamide and IL-12 Treatment Requires Both NK and NK T Cells and Is Associated with the Induction of a Novel NK T Cell Population J. Immunol., September 1, 2001; 167(5): 2569 - 2576. [Abstract] [Full Text] [PDF]
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 M. J. Smyth, N. Y. Crowe, and D. I. Godfrey NK cells and NKT cells collaborate in host protection from methylcholanthrene-induced fibrosarcoma Int. Immunol., April 1, 2001; 13(4): 459 - 463. [Abstract] [Full Text] [PDF]
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M. J. Smyth, E. Cretney, K. Takeda, R. H. Wiltrout, L. M. Sedger, N. Kayagaki, H. Yagita, and K. Okumura Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) Contributes to Interferon {{gamma}}-dependent Natural Killer Cell Protection from Tumor Metastasis J. Exp. Med., March 12, 2001; 193(6): 661 - 670. [Abstract] [Full Text] [PDF]
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