Abstract
CD1d is expressed on APCs and presents glycolipids to CD1d-restricted NKT cells. For the first time, we demonstrate the ability of anti-CD1d mAbs to inhibit the growth of different CD1d-negative experimental carcinomas in mice. Anti-CD1d mAbs systemically activated CD1d(+) APC, as measured by production of IFN-gamma and IL-12. Tumor growth inhibition was found to be completely dependent on IFN-gamma and IL-12 and variably dependent on CD8(+) T cells and NK cells, depending upon the tumor model examined. Anti-CD1d mAb induced greater CD8(+) T cell-dependent tumor suppression where regulatory CD1d-restricted type II NKT cells have been implicated, and were less effective in a NK cell-dependent manner against tumors where T regulatory cells were immunosuppressive. The ability of anti-CD1d mAbs to coincidently activate CD1d(+) APCs to release IL-12 and inhibit CD1d-restricted type II NKT cells makes CD1d an exciting new target for immunotherapy of cancer based on tumor immunoregulation.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Blocking / physiology
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Antibodies, Blocking / therapeutic use*
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Antigen-Presenting Cells / immunology
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Antigen-Presenting Cells / metabolism
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Antigens, CD1d / biosynthesis
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Antigens, CD1d / immunology*
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Antigens, CD1d / metabolism*
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Antineoplastic Agents / immunology
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Antineoplastic Agents / metabolism
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Antineoplastic Agents / therapeutic use*
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Cell Line, Tumor
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Cells, Cultured
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Female
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Growth Inhibitors / biosynthesis
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Growth Inhibitors / immunology
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Growth Inhibitors / therapeutic use*
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Interferon-gamma / biosynthesis
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Interferon-gamma / physiology
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Interleukin-12 / biosynthesis
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Interleukin-12 / physiology
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Mice
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Mice, Inbred BALB C
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Mice, Knockout
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Mice, SCID
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Natural Killer T-Cells / immunology
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Natural Killer T-Cells / metabolism
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Natural Killer T-Cells / pathology
Substances
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Antibodies, Blocking
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Antigens, CD1d
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Antineoplastic Agents
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Growth Inhibitors
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Interleukin-12
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Interferon-gamma