Impact of killer-immunoglobulin-like receptor and human leukocyte antigen genotypes on the efficacy of immunotherapy in acute myeloid leukemia

Leukemia
Elin BernsonFredrik B Thorén

Abstract

Interactions between killer-immunoglobulin-like receptors (KIRs) and their HLA class I ligands are instrumental in natural killer (NK) cell regulation and protect normal tissue from NK cell attack. Human KIR haplotypes comprise genes encoding mainly inhibitory receptors (KIR A) or activating and inhibitory receptors (KIR B). A substantial fraction of humans lack ligands for inhibitory KIRs (iKIRs), that is, a 'missing ligand' genotype. KIR B/x and missing ligand genotypes may thus give rise to potentially autoreactive, unlicensed NK cells. Little is known regarding the impact of such genotypes in untransplanted acute myeloid leukemia (AML). For this study, NK cell phenotypes and KIR/HLA genotypes were determined in 81 AML patients who received immunotherapy with histamine dihydrochloride and low-dose IL-2 for relapse prevention (NCT01347996). We observed that presence of unlicensed NK cells impacted favorably on clinical outcome, in particular among patients harboring functional NK cells reflected by high expression of the natural cytotoxicity receptor (NCR) NKp46. Genotype analyses suggested that the clinical benefit of high NCR expression was restricted to patients with a missing ligand genotype and/or a KIR B/x genotype. The...Continue Reading

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Citations

Jul 11, 2018·Seminars in Immunopathology·Morten Orebo Holmström, Hans Carl Hasselbalch
Jul 30, 2017·Immunology·Francesco Colucci, James Traherne
Oct 6, 2021·Pharmacology Research & Perspectives·María de la Paz SarasolaVanina A Medina

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Methods Mentioned

BETA
flow cytometry
genotyping

Clinical Trials Mentioned

NCT01347996

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