CD1d Activation and Blockade: A New Antitumor Strategy

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 produc...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2009-03, Vol.182 (6), p.3366-3371
Main Authors: Teng, Michele W. L, Yue, Simon, Sharkey, Janelle, Exley, Mark A, Smyth, Mark J
Format: Article
Language:English
Subjects:
Animals
Antibodies, Blocking - physiology
Antibodies, Blocking - therapeutic use
Antigen-Presenting Cells - immunology
Antigen-Presenting Cells - metabolism
Antigens, CD1d - biosynthesis
Antigens, CD1d - immunology
Antigens, CD1d - metabolism
Antineoplastic Agents - immunology
Antineoplastic Agents - metabolism
Antineoplastic Agents - therapeutic use
Cell Line, Tumor
Cells, Cultured
Female
Growth Inhibitors - biosynthesis
Growth Inhibitors - immunology
Growth Inhibitors - therapeutic use
Interferon-gamma - biosynthesis
Interferon-gamma - physiology
Interleukin-12 - biosynthesis
Interleukin-12 - physiology
Mice
Mice, Inbred BALB C
Mice, Knockout
Mice, SCID
Natural Killer T-Cells - immunology
Natural Killer T-Cells - metabolism
Natural Killer T-Cells - pathology
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.0802964