Immunology and immunotherapy of graft-versus-host disease

Abstract

Hematopoietic stem cell transplantation (HSCT) is an important treatment for patients with a variety of malignancies and autoimmune diseases. A common complication after transplantation is graft-versus-host disease (GVHD). This fulminant inflammation arises after the preconditioning regime and causes tissue damage in the host. In this proinflammatory environment, allogeneic donor cells become activated and specifically attack cells of the gut, liver, and skin causing the typical symptoms of GVHD. Even with strong preventive immunosuppression, up to 50 % of patients develop GVHD which requires intensified treatment. However, standard therapy with steroids and calcineurin inhibitors often cannot abrogate GVHD completely, and toxic side effects are usually dose-limiting. Current generalized immunosuppression increases the risk of opportunistic infections as well as relapse of the underlying malignant disease. The graft-versus-tumor effect (GVT) is an important factor for the success of stem cell transplantation and relies on similar mechanisms as GVHD. New therapeutic approaches therefore aim at targeting GVHD more specifically without affecting the GVT response. These include monoclonal antibodies directed against cytokines and signaling pathways involved in the pathogenesis of GVHD. A novel treatment is the adoptive transfer of immunosuppressive cells. Clinical trials are currently ongoing to identify the optimal strategy for the treatment of GVHD.