title: The complex and central role of interferon-γ in graft-versus-host disease and graft-versus-tumor activity.
abstract: Allogeneic hematopoietic cell transplantation (allo-HCT) is increasingly being performed to treat patients with hematologic malignancies. However, separating the beneficial graft-versus-tumor (GVT) or graft-versus-leukemia effects from graft-versus-host disease (GVHD) has been difficult and remains a significant challenge toward improving therapeutic efficacy and reducing toxicity of allo-HCT. GVHD is induced by donor T cells that also mediate potent anti-tumor responses. However, despite the largely shared effector mechanisms, extensive animal studies have demonstrated the potential of dissociating the GVT effect from GVHD. Also in many clinical cases, long-term remission was achieved following allo-HCT, without significant GVHD. A better mechanistic understanding of the immunopathophysiology of GVHD and GVT effects may potentially help to improve allo-HCT as well as maximize the benefit of GVT effects while minimizing GVHD. In this article, we review the role of IFN-γ in regulation of alloresponses following allo-HCT, with a focus on the mechanisms of how this cytokine may separate GVHD from GVT effects.
authors: Columbia Center for Translational Immunology, Columbia University College of Physicians and Surgeons, New York, NY, USA.
authors: Hui
authors: H
authors: Wang
authors: Yong-Guang
authors: YG
authors: Yang
mesh_terms: D000818:Animals; D006086:Graft vs Host Disease / Q000276:immunology* / Q000378:metabolism; D020350:Graft vs Tumor Effect / Q000276:immunology*; D019337:Hematologic Neoplasms / Q000276:immunology / Q000378:metabolism / Q000601:surgery*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: C573415:IFNG protein, human; D007371:Interferon-gamma
keywords: DLI; GVHD; GVT; IFN-γ; allogeneic hematopoietic cell transplantation; leukemia