Roles of Transforming Growth Factor-β in Graft-versus-Host and Graft-versus-Tumor Effects

Transforming growth factor (TGF)-beta is a pleiotropic cytokine with widespread and profound effects on immune cells. Consequently, it has generated considerable interest in relation to the immunologic outcomes after allogeneic hematopoietic cell transplantation. The TGF-beta pathway has been shown to be an important modulator of alloimmunity, with direct consequences on graft-versus-host disease pathophysiology and graft-versus-tumor response. The TGF-beta related effects can be both beneficial and detrimental to the host, underscoring the complexity of TGF-beta biology. This article reviews the evidence linking TGF-beta to alloimmune responses in allogeneic hematopoietic cell transplantation and highlights foreseeable strategies that would maximize the beneficial effects of TGF-beta pathway modulation on both graft-versus-host disease pathophysiology and the graft-versus-tumor effect. Biol Blood Marrow Transplant 18: 1329-1340 (2012) (C) 2012 American Society for Blood and Marrow Transplantation