HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Karnbach, C. Articles by Nakamura, M. C. Search for Related Content PubMed PubMed Citation Articles by Karnbach, C. Articles by Nakamura, M. C.

Immune Rejection of a Large Sarcoma Following Cyclophosphamide and IL-12 Treatment Requires Both NK and NK T Cells and Is Associated with the Induction of a Novel NK T Cell Population¹

Department of Medicine, University of California, San Francisco, CA 94143; and Veterans Administration Medical Center, San Francisco, CA 94121

Combined immunotherapy with cyclophosphamide (Cy) and IL-12, but not IL-12 alone, stimulates eradication of a large established solid tumor (20 mm), MCA207, a methylcholanthrene-induced murine sarcoma. In these studies we demonstrate that NK1.1⁺ cells and CD1d-dependent NK T cells each play important yet distinct roles in regression of a large tumor in response to Cy and IL-12, and we define a novel NK T cell subset, selectively increased by this treatment. Mice depleted of NK1.1⁺ cells demonstrated more rapid initial tumor growth and prolonged tumor regression following treatment, but tumors were eventually eradicated. In contrast, initial tumor regression following therapy was unimpaired in CD1d^-/- mice, which are deficient in most NK T cells, but tumors recurred. No tumor regression occurred following Cy and IL-12 therapy in CD1d^-/- mice that were depleted of NK1.1⁺ cells. We found that Cy and IL-12 induced the selective increase in liver and spleen lymphocytes of a unique NK T subpopulation (DX5⁺NK1.1^-CD3⁺). These cells were not induced by treatment in CD1d^-/- mice. Our studies demonstrate a contribution of both NK and NK T cells to the Cy- and IL-12-stimulated anti-tumor response. We describe the selective induction of a distinct NK T cell subset by Cy and IL-12 therapy, not seen following IL-12 therapy alone, which we suggest may contribute to the successful anti-tumor response induced by this immunotherapeutic regimen.

This article has been cited by other articles:

				D. G. Pellicci, K. J. L. Hammond, J. Coquet, K. Kyparissoudis, A. G. Brooks, K. Kedzierska, R. Keating, S. Turner, S. Berzins, M. J. Smyth, et al. DX5/CD49b-Positive T Cells Are Not Synonymous with CD1d-Dependent NKT Cells J. Immunol., October 1, 2005; 175(7): 4416 - 4425. [Abstract] [Full Text] [PDF]

				J. E. Gumperz CD1d-restricted "NKT" cells and myeloid IL-12 production: an immunological crossroads leading to promotion or suppression of effective anti-tumor immune responses? J. Leukoc. Biol., August 1, 2004; 76(2): 307 - 313. [Abstract] [Full Text] [PDF]

				K. Adachi, H. Tsutsui, E. Seki, H. Nakano, K. Takeda, K. Okumura, L. Van Kaer, and K. Nakanishi Contribution of CD1d-unrestricted hepatic DX5+ NKT cells to liver injury in Plasmodium berghei-parasitized erythrocyte-injected mice Int. Immunol., June 1, 2004; 16(6): 787 - 798. [Abstract] [Full Text] [PDF]

				M. L. Salem, A. N. Kadima, Y. Zhou, C. L. Nguyen, M. P. Rubinstein, M. Demcheva, J. N. Vournakis, D. J. Cole, and W. E. Gillanders Paracrine Release of IL-12 Stimulates IFN-{gamma} Production and Dramatically Enhances the Antigen-Specific T Cell Response after Vaccination with a Novel Peptide-Based Cancer Vaccine J. Immunol., May 1, 2004; 172(9): 5159 - 5167. [Abstract] [Full Text] [PDF]

				Y. Yang, A. Ueno, M. Bao, Z. Wang, J. S. Im, S. Porcelli, and J.-W. Yoon Control of NKT Cell Differentiation by Tissue-Specific Microenvironments J. Immunol., December 1, 2003; 171(11): 5913 - 5920. [Abstract] [Full Text] [PDF]

				S.-H. Park, T. Kyin, A. Bendelac, and C. Carnaud The Contribution of NKT Cells, NK Cells, and Other {gamma}-Chain-Dependent Non-T Non-B Cells to IL-12-Mediated Rejection of Tumors J. Immunol., February 1, 2003; 170(3): 1197 - 1201. [Abstract] [Full Text] [PDF]

				J. G. Segal, N. C. Lee, Y. L. Tsung, J. A. Norton, and K. Tsung The Role of IFN-{gamma} in Rejection of Established Tumors by IL-12 : Source of Production and Target Cancer Res., August 15, 2002; 62(16): 4696 - 4703. [Abstract] [Full Text] [PDF]

				N. Y. Crowe, M. J. Smyth, and D. I. Godfrey A Critical Role for Natural Killer T Cells in Immunosurveillance of Methylcholanthrene-induced Sarcomas J. Exp. Med., July 1, 2002; 196(1): 119 - 127. [Abstract] [Full Text] [PDF]