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 in...

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Bibliographic Details
Published in:Best practice & research. Clinical haematology 2016-12, Vol.29 (4), p.351-358
Main Authors: Shaffer, Brian C, Hsu, Katharine C
Format: Article
Language:English
Subjects:
Acute myelogenous leukemia
Allo HCT
Allogeneic hematopoietic cell transplantation
Allografts
Alloreactivity
AML
Graft versus host disease
Graft versus leukemia
Graft vs Host Disease - immunology
Graft vs Host Disease - therapy
Graft vs Leukemia Effect - immunology
GVHD
GVL
Hematology, Oncology and Palliative Medicine
Hematopoietic Stem Cell Transplantation
Humans
Killer Cells, Natural - immunology
Killer Cells, Natural - transplantation
Killer Ig-like receptors
KIR
Leukemia, Myeloid, Acute - immunology
Leukemia, Myeloid, Acute - therapy
Lymphocyte Transfusion
Natural killer
Receptors, KIR - immunology
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Summary: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.
ISSN:1521-6926
1532-1924
DOI:10.1016/j.beha.2016.10.010