Targeting Cytokines in GVHD Therapy

Transplantation of donor-derived allogeneic hematopoietic cells causes increased survival in patients suffering from various blood cancers and other hematologic and immunologic diseases. However, this health benefit is limited to certain patients. One major complication is graft-versus-host disease (GVHD) that occurs when donor-derived immune cells recognize host cells/tissues as foreign and perpetrate subsequent destruction. Cytokines are a major class of effector molecules that are involved in GVHD pathogenesis. Proinflammatory cytokines released by activated immune cells including T cells lead to the onset of GVHD. T cell depletion (TCD) is an effective approach for GVHD prevention. Several immune suppressive drugs are also used to treat GVHD. However, these prophylactic and treatment strategies often lead to an immune compromised state that increases the risk for infection and cancer relapse. Considering the adverse effects of TCD and overall immune suppression, more selective managements such as approaches targeting proinflammatory cytokines have emerged as a promising strategy to control GVHD. Therefore, this work is dedicated to review recent development in the studies of cytokines and their future implication in GVHD therapy.