title: How important is NK alloreactivity and KIR in allogeneic transplantation?
abstract: Relapse of acute myelogenous leukemia (AML) after allogeneic hematopoietic cell transplantation (allo HCT) is a major cause of death in transplant recipients. Efforts to control relapse by promoting donor T-cell alloreactivity, such as withdrawal of immune suppression or donor lymphocyte infusions, are limited by the propensity to induce graft versus host disease (GVHD) and by inadequate efficacy. Therefore, options for AML patients who have relapsed AML after allo HCT are few and outcomes are poor. Similar to T-cells, natural killer (NK) cells have potent anti-leukemia effector capacity, and yet unlike T-cells, NK cells do not mediate GVHD. Furthermore, their function does not require matching of human leukocyte antigens (HLA) between donor and recipient. Maximizing donor NK alloreactivity thus holds the exciting possibility to induce the graft versus leukemia (GVL) effect without engendering GVHD. Among the array of activating and inhibitory NK cell surface receptors, the killer Ig-like receptors (KIR) play a central role in modulating NK effector function. Here we will review how KIR mediates donor alloreactivity, discuss the role of KIR gene and allele typing to optimize allo HCT donor selection, and discuss how KIR may aid adoptive NK and other cell therapies.
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States; Department of Medicine, Weill Cornell Medical College, New York, NY, United States.
authors.forename: Brian C
authors.initials: BC
authors.lastname: Shaffer
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States; Immunology Program, Sloan Kettering Institute, New York, NY, United States; Department of Medicine, Weill Cornell Medical College, New York, NY, United States. Electronic address: hsuk@mskcc.org.
authors.forename: Katharine C
authors.initials: KC
authors.lastname: Hsu
mesh_terms: D064591:Allografts; D006086:Graft vs Host Disease / Q000276:immunology / Q000628:therapy*; D020544:Graft vs Leukemia Effect / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000637:transplantation*; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000628:therapy*; D017710:Lymphocyte Transfusion; D054340:Receptors, KIR / Q000276:immunology*
chemical_list: D054340:Receptors, KIR
keywords: AML; Acute myelogenous leukemia; Allo HCT; Allogeneic hematopoietic cell transplantation; Alloreactivity; GVHD; GVL; Graft versus host disease; Graft versus leukemia; KIR; Killer Ig-like receptors; NK; Natural killer