Dichotomous Role of Interferon-γ in Allogeneic Bone Marrow Transplant

• Type of Material: Article
• Authors: Ying Lu, Emory University; Edmund K Waller, Emory University
• Language: English
• Date: 2009-11
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2009 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.bbmt.2009.07.015
• Title of Journal or Parent Work: Biology of Blood and Marrow Transplantation
• ISSN: 1083-8791
• Volume: 15
• Issue: 11
• Start Page: 1347
• End Page: 1353
• Grant/Funding Information: This work was supported in part by National Institutes of Health Grant R01 CA074364 to E.K. Waller.
• Keywords: Graft-versus-leukemia; Graft-versus-host disease; IFN-γ; Allogeneic bone marrow transplant
• Research Categories: Health Sciences, Oncology

Abstract

Interferon (IFN)-γ is a pleiotropic cytokine with a central role in innate and adaptive immunity. As a potent pro-inflammatory and anti-tumor cytokine, IFN-γ is conventionally thought to be responsible for driving cellular immune response. On the other hand, accumulating evidence suggests that IFN-γ also has immuno-suppressive activity. An important role for IFN-γ in inhibiting graft-versus-host disease (GVHD) has been demonstrated in murine models, in spite of IFN-γ being one of the key factors amplifying T cell activation during the process of acute GVHD, the major complication and cause of post-transplant mortality in allogeneic bone marrow transplantation (BMT). At the same time, IFN-γ facilitates graft-versus-leukemia (GVL) activity. Dissociation of GVL effects from GVHD has been the ultimate goal of allogeneic BMT in the treatment of hematological malignancies. This paradoxical role of IFN-γ makes modulating its activity a promising strategy to maximize GVL while minimizing GVHD and improve clinical outcomes in BMT. In this review, the effects of IFN-γ on GVHD and GVL are discussed with consideration of the mechanism of IFN-γ action.