Human NK cells: from HLA class I-specific killer Ig-like receptors to the therapy of acute leukemias

Over the past 20 years, major progress has been made in our understanding of natural killer (NK) cells. It has become clear that NK cells are regulated by a number of receptors with opposite functions that finely tune potent effector functions such as cytolytic activity and release of cytokines that play a major role in inflammation and immunoregulation. This review traces the major advances in human NK cell biology from the original discovery of human leukocyte antigen class I-specific inhibitory receptors to recent groundbreaking clinical applications. These, in turn, led to major achievements and further expectations in the cure of high risk of otherwise fatal leukemias. It has become evident that there is a role of donor-derived 'alloreactive' NK cells in eradicating acute myeloid (and now also lymphoid) leukemias in the T-cell-depleted haploidentical hemopoietic stem cell transplantation setting. The key role played also in preventing graft rejection and graft versus host disease renders alloreactive NK cells an ideal tool for successful haploidentical hematopoietic stem cell transplantation.