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CD1d Activation and Blockade: A New Antitumor Strategy¹

Michele W. L. Teng^*,, Simon Yue, Janelle Sharkey^*, Mark A. Exley and Mark J. Smyth^2,*,

^* Cancer Immunology Program, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia; Beth Israel Deaconess Medical Center, Boston, MA, 02215; and Department of Pathology, University of Melbourne, Parkville, Australia

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- and IL-12. Tumor growth inhibition was found to be completely dependent on IFN- 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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ We thank the National Health and Medical Research Council (NHMRC) of Australia for the support of a Program Grant, a Research Fellowship (to M.J.S.), and a Doherty Fellowship (to M.W.L.T.). We also thank the Cancer Council of Victoria for Project Grant Support. M.A.E. was supported by NIH DK066917.

² Address correspondence and reprint requests to Professor Mark J. Smyth, Cancer Immunology Program, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia. E-mail address: mark.smyth{at}petermac.org

³ Abbreviations used in this paper: DC, dendritic cell; -GC, -galactosylceramide; anti-ASGM1, anti-asialo GM1; WT, wild type; cIg, control Ig.

This article has been cited by other articles:

				M. W. L. Teng, J. Sharkey, N. M. McLaughlin, M. A. Exley, and M. J. Smyth CD1d-Based Combination Therapy Eradicates Established Tumors in Mice J. Immunol., August 1, 2009; 183(3): 1911 - 1920. [Abstract] [Full Text] [PDF]