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 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.
Teng
Michele W L
MW
Cancer Immunology Program, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
Yue
Simon
S
Sharkey
Janelle
J
Exley
Mark A
MA
Smyth
Mark J
MJ
D000818:Animals; D019138:Antibodies, Blocking / Q000502:physiology / Q000627:therapeutic use*; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D055610:Antigens, CD1d / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D005260:Female; D006131:Growth Inhibitors / Q000096:biosynthesis / Q000276:immunology / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000502:physiology; D018664:Interleukin-12 / Q000096:biosynthesis / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D016513:Mice, SCID; D055611:Natural Killer T-Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D019138:Antibodies, Blocking; D055610:Antigens, CD1d; D000970:Antineoplastic Agents; D006131:Growth Inhibitors; D018664:Interleukin-12; D007371:Interferon-gamma