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Prepublished online as a Blood First Edition Paper on June 5, 2003; DOI 10.1182/blood-2002-12-3949. This Article 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 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. Social Bookmarking                   What's this? Submitted December 31, 2002 Accepted May 25, 2003 Anti-tumor 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* Bone Marrow Transplantation Section, Transplantation Biology Research Center, Boston, MA, USA Department of Hematology, Humboldt University, Berlin, Germany * Corresponding author; email: megan.sykes{at}tbrc.mgh.harvard.edu. Some patients lose chimerism following non-myeloablative hematopoietic cell transplantation (HCT), yet, surprisingly, enjoy sustained tumor remissions. We hypothesized that host-vs-graft (HVG) alloresponses might induce anti-tumor effects against recipient tumors. We explored this question in mice by administering recipient leukocyte infusions (RLI) to mixed chimeras established with non-myeloablative conditioning. Mixed chimeras were prepared in the B10.A (H2a)B6 (H2b) strain combination using depleting anti-T cell 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-host-disease (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 anti-tumor effects against the host-type B-cell lymphoma A20. HCT was essential for the anti-tumor effect of RLI. RLI-induced elevated serum IFN- levels, and recipient-derived IFN- was critical for their anti-tumor effects. Thus, HVG reactions (spontaneous or induced by RLI) mediate anti-tumor 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. 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