Role of natural killer cells in hematopoietic stem cell transplantation: myth or reality?

Natural killer (NK) cells play a crucial role in the innate immune system and are responsible for the initial responses in the surveillance against malignant cells and virally infected cells. NK cells express their own repertoire of receptors, including activating and inhibitory receptors, which bind to major histocompatibility complex class I or class-I-related molecules. Binding of NK cell inhibitory receptors to their major histocompatibility complex class I ligands protects the target cells from NK cell-mediated cytotoxicity. NK cell alloreactivity has been put to use in allogeneic hematopoietic stem cell transplantation to reduce the rate of relapse and of graft-versus-host disease. A variety of findings have been observed in clinical studies, showing either beneficial or deleterious effects on clinical outcome. This article reviews the results of major clinical trials in relation to the model used to define NK cell alloreactivity.