Dichotomous role of interferon-gamma in allogeneic bone marrow transplant.
Interferon (IFN)-gamma is a pleiotropic cytokine with a central role in innate and adaptive immunity. As a potent pro-inflammatory and antitumor cytokine, IFN-gamma is conventionally thought to be responsible for driving cellular immune response. On the other hand, accumulating evidence suggests that IFN-gamma also has immunosuppressive activity. An important role for IFN-gamma in inhibiting graft-versus-host disease (GVHD) has been demonstrated in murine models, despite IFN-gamma being one of the key factors amplifying T cell activation during the process of acute GVHD (aGVHD), the major complication and cause of post-transplant mortality in allogeneic bone marrow transplantation (BMT). At the same time, IFN-gamma facilitates graft-versus-leukemia (GVL) activity. Dissociation of GVL effects from GVHD has been the ultimate goal of allogeneic BMT in the treatment of hematologic malignancies. This paradoxic role of IFN-gamma 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-gamma on GVHD and GVL are discussed with consideration of the mechanism of IFN-gamma action.
Lu
Ying
Y
Department of Hematology/Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia 30322, USA.
Waller
Edmund K
EK
D000818:Animals; D000938:Antigen-Presenting Cells / Q000637:transplantation; D016026:Bone Marrow Transplantation / Q000276:immunology*; D004334:Drug Administration Schedule; D004790:Enzyme Induction / Q000187:drug effects; D006086:Graft vs Host Disease / Q000276:immunology* / Q000517:prevention & control; D020544:Graft vs Leukemia Effect / Q000276:immunology*; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D007371:Interferon-gamma / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000378:metabolism; D007942:Leukemia, Experimental / Q000188:drug therapy / Q000276:immunology / Q000601:surgery; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000378:metabolism; D014184:Transplantation, Homologous / Q000276:immunology
D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma