Natural Killer Cells and Killer-Cell Immunoglobulin-Like Receptor Polymorphisms: Their Role in Hematopoietic Stem Cell Transplantation

Abstract

Natural killer (NK) cells are important effector cells in the early control of infected, malignant, and "nonself" cells. Various receptor families are involved in enabling NK cells to detect and efficiently eliminate these target cells. The killer-cell immunoglobulin-like receptor (KIR) family is a set of receptors that are very polymorphic with regard to gene content, expression level, and expression pattern. KIRs are responsible for the induction of a NK cell alloreactive response through their interaction with HLA class I molecules. The role of NK cells in hematopoietic stem cell transplantation (HSCT) has been studied for many years, and induction of antileukemic responses by donor NK cells has been reported. Conflicting data still exist on the exact circumstances in which the KIR repertoire affects and influences clinical outcome after HSCT. More large-scale studies are needed on well-defined cohorts to unravel the mechanism of action of the NK cell-mediated alloresponse in an HSCT setting.

Relevance of Polymorphic KIR and HLA Class I Genes in NK-Cell-Based Immunotherapies for Adult Leukemic Patients

“…The following two digits are used to distinguish alleles that only differ in synonymous (noncoding) substitutions within the coding sequence (2DL1*00302), and the last two digits are used to distinguish alleles that only differ in substitutions in noncoding regions (2DL1*0030202). For more than 15 years, specific KIR primers, probes or sequence-based-typing (SBT) methods have been used to assign KIR alleles of limited KIR genes [40]. More recently, next-generation sequencing (NGS) technologies have permitted the assignment of the alleles of all KIR genes [41][42][43].…”

Natural Killer Cells Differentiate Human Adipose-Derived Stem Cells and Modulate Their Adipogenic Potential

“…2,3 Although they were originally named for their ability to mediate spontaneous (i.e., "natural") cytotoxicity using the release of lytic enzymes, natural killer cells are also prolific secretors of cytokines and chemokines, including interferon-γ, tumor necrosis factor-α, and granulocyte-macrophage colony-stimulating factor. 4,5 Recent advances in the field of tumor immunology have implicated natural killer cells as being intimately involved in the selection of certain cancer stem cell populations.…”