Abstract
Both invariant natural killer T (NK T) cells and CD4(+)CD25(+) T regulatory cells (T(regs)) regulate the immune system to maintain homeostasis. In a tumour setting, NK T cells activated by alpha-galactosylceramide (alpha-GalCer) execute anti-tumour activity by secreting cytokines. By contrast, T(regs) intrinsically suppress antigen-specific immune responses and are often found to be elevated in tumour patients. In this study, we have shown that T(regs) regulate NK T cell function negatively in vitro, suggesting a direct interaction between these cell types. In a murine mammary tumour model, we demonstrated that administration of either alpha-GalCer or anti-CD25 antibody alone markedly suppressed tumour formation and pulmonary metastasis, and resulted in an increase in the survival rate up to 44% (from a baseline of 0%). When treatments were combined, depletion of T(regs) boosted the anti-tumour effect of alpha-GalCer, and the survival rate jumped to 85%. Our results imply a potential application of combining T(reg) cell depletion with alpha-GalCer to stimulate NK T cells for cancer therapy.
Publication types
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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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Antibodies, Monoclonal / therapeutic use
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Dendritic Cells / immunology
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Disease Models, Animal
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Female
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Galactosylceramides / immunology
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Galactosylceramides / therapeutic use
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Immunity, Cellular / immunology*
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Interferon-gamma / metabolism
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Interleukin-2 Receptor alpha Subunit / immunology*
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Lung Neoplasms / pathology
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Lung Neoplasms / prevention & control
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Lung Neoplasms / secondary
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Lymphocyte Activation / immunology
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Lymphocyte Depletion*
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Mammary Neoplasms, Experimental / immunology*
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Mammary Neoplasms, Experimental / pathology
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Mammary Neoplasms, Experimental / therapy*
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Natural Killer T-Cells / immunology*
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Natural Killer T-Cells / metabolism
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Survival Rate
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T-Lymphocytes, Regulatory / cytology
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T-Lymphocytes, Regulatory / drug effects
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T-Lymphocytes, Regulatory / immunology*
Substances
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Antibodies, Monoclonal
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Galactosylceramides
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Il2ra protein, mouse
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Interleukin-2 Receptor alpha Subunit
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alpha-galactosylceramide
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Interferon-gamma