Biology and clinical effects of natural killer cells in allogeneic transplantation

• Published in: Current opinion in oncology Vol. 22; no. 2; p. 130
• Main Authors: Benjamin, Jonathan E, Gill, Saar, Negrin, Robert S
• Format: Journal Article
• Language: English
• Published: United States 01.03.2010
• Subjects: Clinical Trials as Topic; Hematopoietic Stem Cell Transplantation; Humans; Killer Cells, Natural - immunology; Killer Cells, Natural - transplantation; Transplantation, Homologous - immunology
• ISSN: 1531-703X
• DOI: 10.1097/CCO.0b013e328335a559

Following allogeneic hematopoietic cell transplantation, donor-derived natural killer (NK) cells target recipient hematopoietic cells, resulting in an antileukemia effect and a lower incidence of graft rejection. NK cells do not mediate and may diminish graft versus host disease. Here we review the determinants of NK cell alloreactivity and their implications for adoptive NK cell therapy. NK cell alloreactivity has been defined by the absence of recipient MHC class I ligands for donor inhibitory killer immunoglobulin-like receptor (KIR) receptors, as predicted by a number of algorithms. Recently, the role of activating NK receptors and their cognate ligands has received more attention. The beneficial clinical effect of NK-cell alloreactivity has not been uniformly demonstrated, likely reflecting differences in conditioning regimens, graft components and posttransplant immune suppression. Investigations of NK cell phenotype and function after transplantation have helped demonstrate which NK cell subsets mediate the graft versus leukemia effect. These advances have proceeded in parallel with increasing facility in GMP-grade bulk purification and administration of NK cell preparations. NK cells are a heterogeneous population of lymphocytes with diverse patterns of target-cell recognition and effector function. Further clinical and functional correlations will help maximize their potential for clinical benefit.