This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend 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 Wang, L.-X. Articles by Hu, H.-M. Search for Related Content PubMed PubMed Citation Articles by Wang, L.-X. Articles by Hu, H.-M.

Interleukin-7-Dependent Expansion and Persistence of Melanoma-Specific T Cells in Lymphodepleted Mice Lead to Tumor Regression and Editing

¹ Laboratory of Cancer Immunobiology; ² Laboratory of Molecular and Tumor Immunology; ³ Robert W. Franz Cancer Center, Earle A. Chiles Research Institute, Providence Portland Medical Center, Portland, Oregon; ⁴ Department of Microbiology and Immunology, School of Medicine, Southeast University, Nanjing, Jiangsu; ⁵ Department of Immunology, Shanghai Medical School of Fudan University, Shanghai, China; and ⁶ National Cancer Institute, NIH, Bethesda, Maryland

Requests for reprints: Hong-Ming Hu, Laboratory of Cancer Immunobiology, Providence Portland Medical Center, Robert W. Franz Cancer Center, Earle A. Chiles Research Institute, 4805 Northeast Glisan Street, Portland, OR 97213. Phone: 503-215-6531; Fax: 503-215-6841; E-mail: hhu{at}providence.org.

Active-specific immunotherapy with dendritic cells loaded with peptide derived from the melanoma antigen, gp100, failed to mediate regression of established B16F10 melanoma in normal mice. Dendritic cell vaccination induced activation and subsequent deletion of adoptively transferred naive CD8⁺ T-cell receptor transgenic (pmel-1) T cells specific for gp100 in normal mice. In lymphodepleted mice, dendritic cell vaccination produced greater T-cell expansion, long-term persistence of memory T cells, and tumor regression. Most tumors that persisted in the presence of functional memory T cells had either lost or exhibited reduced expression of MHC class I or gp100 proteins. In contrast to other naive T cells, pmel-1 T cells adoptively transferred to lymphodepleted mice exhibited faster proliferation and a more differentiated phenotype after exposure to peptide-pulsed dendritic cells. Proliferation and persistence of pmel-1 T cells was highly dependent on interleukin-7 (IL-7) in irradiated mice, and IL-15 when IL-7 was neutralized, two critical homeostatic cytokines produced in response to the irradiation-induced lymphodepletion.

This article has been cited by other articles:

				C. A. Klebanoff, Z. Yu, L. N. Hwang, D. C. Palmer, L. Gattinoni, and N. P. Restifo Programming tumor-reactive effector memory CD8+ T cells in vitro obviates the requirement for in vivo vaccination Blood, August 27, 2009; 114(9): 1776 - 1783. [Abstract] [Full Text] [PDF]

				M. Sakaguchi, K. Kataoka, F. Abarzua, R. Tanimoto, M. Watanabe, H. Murata, S. S. Than, K. Kurose, Y. Kashiwakura, K. Ochiai, et al. Overexpression of REIC/Dkk-3 in Normal Fibroblasts Suppresses Tumor Growth via Induction of Interleukin-7 J. Biol. Chem., May 22, 2009; 284(21): 14236 - 14244. [Abstract] [Full Text] [PDF]

				W. Jing, J. A. Gershan, and B. D. Johnson Depletion of CD4 T cells enhances immunotherapy for neuroblastoma after syngeneic HSCT but compromises development of antitumor immune memory Blood, April 30, 2009; 113(18): 4449 - 4457. [Abstract] [Full Text] [PDF]

				M. L. Salem, C. M. Diaz-Montero, A. A. Al-Khami, S. A. El-Naggar, O. Naga, A. J. Montero, A. Khafagy, and D. J. Cole Recovery from Cyclophosphamide-Induced Lymphopenia Results in Expansion of Immature Dendritic Cells Which Can Mediate Enhanced Prime-Boost Vaccination Antitumor Responses In Vivo When Stimulated with the TLR3 Agonist Poly(I:C) J. Immunol., February 15, 2009; 182(4): 2030 - 2040. [Abstract] [Full Text] [PDF]

				X. Chang, P. Zheng, and Y. Liu Homeostatic Proliferation in the Mice with Germline FoxP3 Mutation and its Contribution to Fatal Autoimmunity J. Immunol., August 15, 2008; 181(4): 2399 - 2406. [Abstract] [Full Text] [PDF]

				C. Sportes, F. T. Hakim, S. A. Memon, H. Zhang, K. S. Chua, M. R. Brown, T. A. Fleisher, M. C. Krumlauf, R. R. Babb, C. K. Chow, et al. Administration of rhIL-7 in humans increases in vivo TCR repertoire diversity by preferential expansion of naive T cell subsets J. Exp. Med., July 7, 2008; 205(7): 1701 - 1714. [Abstract] [Full Text] [PDF]

				O. Goldberger, I. Volovitz, A. Machlenkin, E. Vadai, E. Tzehoval, and L. Eisenbach Exuberated Numbers of Tumor-Specific T Cells Result in Tumor Escape Cancer Res., May 1, 2008; 68(9): 3450 - 3457. [Abstract] [Full Text] [PDF]

				T. Suzuki, S. Ogawa, K. Tanabe, H. Tahara, R. Abe, and H. Kishimoto Induction of Antitumor Immune Response by Homeostatic Proliferation and CD28 Signaling J. Immunol., April 1, 2008; 180(7): 4596 - 4605. [Abstract] [Full Text] [PDF]

				J. S. Miller, D. J. Weisdorf, L. J. Burns, A. Slungaard, J. E. Wagner, M. R. Verneris, S. Cooley, R. Wangen, S. K. Fautsch, R. Nicklow, et al. Lymphodepletion followed by donor lymphocyte infusion (DLI) causes significantly more acute graft-versus-host disease than DLI alone Blood, October 1, 2007; 110(7): 2761 - 2763. [Abstract] [Full Text] [PDF]

				C. M. Paulos, A. Kaiser, C. Wrzesinski, C. S. Hinrichs, L. Cassard, A. Boni, P. Muranski, L. Sanchez-Perez, D. C. Palmer, Z. Yu, et al. Toll-like Receptors in Tumor Immunotherapy Clin. Cancer Res., September 15, 2007; 13(18): 5280 - 5289. [Abstract] [Full Text] [PDF]

				E. M. Wall, K. Milne, M. L. Martin, P. H. Watson, P. Theiss, and B. H. Nelson Spontaneous Mammary Tumors Differ Widely in Their Inherent Sensitivity to Adoptively Transferred T Cells Cancer Res., July 1, 2007; 67(13): 6442 - 6450. [Abstract] [Full Text] [PDF]

				X. Yang, Y. Chu, Y. Wang, R. Zhang, and S. Xiong Targeted in vivo expression of IFN-{gamma}-inducible protein 10 induces specific antitumor activity J. Leukoc. Biol., December 1, 2006; 80(6): 1434 - 1444. [Abstract] [Full Text] [PDF]