Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents / administration & dosage*
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Antineoplastic Agents / therapeutic use
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Disease Models, Animal*
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Dose-Response Relationship, Immunologic
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Drug Administration Schedule
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Immunity, Innate / genetics
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Injections, Intraperitoneal
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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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Interleukin-12 / administration & dosage*
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Interleukin-12 / physiology
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Interleukin-12 / therapeutic use
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Killer Cells, Natural / immunology
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Lung Neoplasms / genetics
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Lung Neoplasms / immunology
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Lung Neoplasms / prevention & control
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Lung Neoplasms / secondary
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Lymphocyte Depletion
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Lymphoma / immunology
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Lymphoma / prevention & control
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Male
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Melanoma, Experimental / immunology
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Melanoma, Experimental / prevention & control
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Melanoma, Experimental / secondary
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Membrane Glycoproteins / deficiency
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / physiology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Neoplasm Transplantation
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Perforin
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Pore Forming Cytotoxic Proteins
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Prostatic Neoplasms / immunology
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Prostatic Neoplasms / prevention & control
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T-Lymphocyte Subsets / immunology
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Tumor Cells, Cultured
Substances
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Antineoplastic Agents
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Membrane Glycoproteins
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Pore Forming Cytotoxic Proteins
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Perforin
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Interleukin-12
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Interferon-gamma