The complex and central role of interferon-? in graft-versus-host disease and graft-versus-tumor activity.

Immunological reviews

PubMedID: 24517424

Wang H, Yang YG. The complex and central role of interferon-? in graft-versus-host disease and graft-versus-tumor activity. Immunol Rev. 2014;258(1):30-44.
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-? in regulation of alloresponses following allo-HCT, with a focus on the mechanisms of how this cytokine may separate GVHD from GVT effects.