SEARCH:   Advanced

Prepublished online as a Blood First Edition Paper on June 5, 2003; DOI 10.1182/blood-2002-12-3949. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-12-3949v1 102/6/2300    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Rubio, M.-T. Articles by Sykes, M. Search for Related Content PubMed PubMed Citation Articles by Rubio, M.-T. Articles by Sykes, M. Related Collections Neoplasia Transplantation Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 September 2003, Vol. 102, No. 6, pp. 2300-2307 TRANSPLANTATION Antitumor effect of donor marrow graft rejection induced by recipient leukocyte infusions in mixed chimeras prepared with nonmyeloablative conditioning: critical role for recipient-derived IFN- Marie-Therese Rubio, Yong-Mi Kim, Teviah Sachs, Markus Mapara, Guiling Zhao, and Megan Sykes From the Transplantation Biology Research Center, Bone Marrow Transplantation Section, Massachusetts General Hospital, Boston. Some patients lose chimerism following nonmyeloablative hematopoietic cell transplantation (HCT), yet, surprisingly, enjoy sustained tumor remissions. We hypothesized that host-versus-graft (HVG) alloresponses might induce antitumor effects against recipient tumors. We explored this question in mice by administering recipient leukocyte infusions (RLIs) to mixed chimeras established with nonmyeloablative conditioning. Mixed chimeras were prepared in the B10.A (H2a)B6 (H2b) strain combination using depleting anti–T-cell monoclonal antibodies (mAbs), cyclophosphamide, and thymic irradiation. B6 myeloid leukemia cells (MMB3.19) were administered 7 days following donor lymphocyte infusion (DLI) or RLI on day 35. Conversion to full donor chimerism occurred without graft-versus-hostdisease (GVHD) following DLI, whereas RLI led to loss of chimerism. Both RLI and DLI significantly delayed tumor mortality. In another strain combination (B10.BR [H2k]BALB/c [H2d]), RLI-induced or spontaneous loss of chimerism was associated with antitumor effects against the host-type B-cell lymphoma A20. HCT was essential for the antitumor effect of RLI. RLI induced elevated serum interferon- (IFN-) levels, and recipient-derived IFN- was critical for their antitumor effects. Thus, HVG reactions (spontaneous or induced by RLI) mediate antitumor effects against hematologic malignancies via a recipient-derived IFN-–mediated mechanism. A novel approach to achieving anti-tumor effects without the risk of GVHD is suggested. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y. Kamiryo, M. Eto, H. Yamada, T. Yajima, M. Harano, A. Takeuchi, K. Tatsugami, M. Hamaguchi, S. Naito, and Y. Yoshikai Donor CD4 T Cells Are Critical in Allogeneic Stem Cell Transplantation against Murine Solid Tumor Cancer Res., June 15, 2009; 69(12): 5151 - 5158. [Abstract] [Full Text] [PDF] M. Eto, Y. Kamiryo, A. Takeuchi, M. Harano, K. Tatsugami, M. Harada, K. Kiyoshima, M. Hamaguchi, T. Teshima, M. Tsuneyoshi, et al. Posttransplant Administration of Cyclophosphamide and Donor Lymphocyte Infusion Induces Potent Antitumor Immunity to Solid Tumor Clin. Cancer Res., May 1, 2008; 14(9): 2833 - 2840. [Abstract] [Full Text] [PDF] M. Eto, M. Harano, K. Tatsugami, M. Harada, Y. Kamiryo, K. Kiyoshima, M. Hamaguchi, M. Tsuneyoshi, Y. Yoshikai, and S. Naito Cyclophosphamide-Using Nonmyeloablative Allogeneic Cell Therapy against Renal Cancer with a Reduced Risk of Graft-versus-Host Disease Clin. Cancer Res., February 1, 2007; 13(3): 1029 - 1035. [Abstract] [Full Text] [PDF] T. I. Saito and M. Sykes NK1.1+ Cells Are Involved in the Anti-Tumor Immunity Induced by the Rejection of Donor Hematopoietic Cells in Mixed Bone Marrow Chimeras. Blood (ASH Annual Meeting Abstracts), November 16, 2006; 108(11): 3166 - 3166. [Abstract] [PDF] T. I. Saito and M. Sykes Long-Lasting Anti-Tumor Immunity Induced by the Rejection of Donor Hematopoietic Cells in Mixed Bone Marrow Chimeras. Blood (ASH Annual Meeting Abstracts), November 16, 2005; 106(11): 1319 - 1319. [Abstract] M. Harano, M. Eto, T. Iwai, K. Tatsugami, K. Kiyoshima, Y. Kamiryo, M. Tsuneyoshi, Y. Yoshikai, and S. Naito Renal Cancer Treatment with Low Levels of Mixed Chimerism Induced by Nonmyeloablative Regimen Using Cyclophosphamide in Mice Cancer Res., November 1, 2005; 65(21): 10032 - 10040. [Abstract] [Full Text] [PDF] M.-T. Rubio, T. I. Saito, K. Kattleman, G. Zhao, J. Buchli, and M. Sykes Mechanisms of the Antitumor Responses and Host-versus-Graft Reactions Induced by Recipient Leukocyte Infusions in Mixed Chimeras Prepared with Nonmyeloablative Conditioning: A Critical Role for Recipient CD4+ T Cells and Recipient Leukocyte Infusion-Derived IFN-{gamma}-Producing CD8+ T Cells J. Immunol., July 15, 2005; 175(2): 665 - 676. [Abstract] [Full Text] [PDF] T. R. Spitzer Haploidentical Stem Cell Transplantation: The Always Present but Overlooked Donor Hematology, January 1, 2005; 2005(1): 390 - 395. [Abstract] [Full Text] [PDF] R. Puliaev, P. Nguyen, F. D. Finkelman, and C. S. Via Differential Requirement for IFN-{gamma} in CTL Maturation in Acute Murine Graft-versus-Host Disease J. Immunol., July 15, 2004; 173(2): 910 - 919. [Abstract] [Full Text] [PDF] M. Y. Mapara and M. Sykes Tolerance and Cancer: Mechanisms of Tumor Evasion and Strategies for Breaking Tolerance J. Clin. Oncol., March 15, 2004; 22(6): 1136 - 1151. [Abstract] [Full Text] [PDF]

	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020