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Related Collections Immunotherapy Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 September 2002, Vol. 100, No. 5, pp. 1551-1558 CHEMOKINES Efficacious immunomodulatory activity of the chemokine stromal cell-derived factor 1 (SDF-1): local secretion of SDF-1 at the tumor site serves as T-cell chemoattractant and mediates T-cell-dependent antitumor responses Kyriaki Dunussi-Joannopoulos, Krystyna Zuberek, Kathlene Runyon, Robert G. Hawley, Anthony Wong, Jamie Erickson, Steve Herrmann, and John P. Leonard From Wyeth Research, Cambridge, MA, and Department of Hematopoiesis, Holland Laboratory, American Red Cross, Rockville, MD. The chemokine stromal cell-derived factor 1 (SDF-1) is essential for perinatal viability, B lymphopoiesis, and bone marrow myelopoiesis, and is a potent monocyte and T-lymphocyte chemoattractant. Interactions of SDF-1 with its receptor CXCR4 have been implicated in CD34+ cell migration and homing. Here it is shown that human SDF-1 (hSDF-1) alone secreted by hSDF-1-transduced tumor cells promotes efficacious antitumor responses. The murine C1498 leukemia and B16F1 melanoma models have been studied. For expression of hSDF-1 by tumor cells (SDF-tumor cells), packaging cell lines secreting retroviruses encoding hSDF-1 have been used. The results demonstrate that 50% (B16F1) and 90% (C1498) of naive mice injected with SDF-tumor cells reject their tumors. Prophylactic vaccination of naive mice with irradiated SDF-tumor cells leads to systemic immunity, and therapeutic vaccination leads to cure of established tumors. Mice that previously rejected live SDF-tumor cells are immune to the rejected tumor but susceptible to another tumor and have in vitro tumor-specific cytotoxic T lymphocyte (CTL) activity. SDF-tumor cells are not rejected by immunodeficient scid mice. Immunohistochemistry shows significant infiltration of SDF-1 tumors by T cells, and in vivo T-cell depletion studies indicate that CD4+ T cells are required for SDF-mediated tumor rejection. In conclusion, the present data suggest that SDF-1/CXCR4 interactions have the potential to regulate efficacious antitumor immune responses; exploitation of these interactions may lead to novel therapeutic interventions. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Hyakudomi, T. Matsubara, R. Hyakudomi, T. Yamamoto, S. Kinugasa, A. Yamanoi, R. Maruyama, and T. Tanaka Increased Expression of Fractalkine is Correlated with a Better Prognosis and an Increased Number of Both CD8+ T Cells and Natural Killer Cells in Gastric Adenocarcinoma Ann. Surg. Oncol., June 1, 2008; 15(6): 1775 - 1782. [Abstract] [Full Text] [PDF] I. Kryczek, S. Wei, E. Keller, R. Liu, and W. 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