Killer immunoglobulin-like receptor (KIR) and KIR–ligand genotype do not correlate with clinical outcome of renal cell carcinoma patients receiving high-dose IL2

Abstract

NK cells play a role in many cancer immunotherapies. NK cell activity is tightly regulated by killer immunoglobulin-like receptor (KIR) and KIR–ligand interactions. Inhibitory KIR–ligands have been identified as HLA molecules, while activating KIR–ligands are largely unknown. Individuals that have not inherited the corresponding KIR–ligand for at least one inhibitory KIR gene are termed the “KIR–ligand missing” genotype, and they are thought to have a subset of NK cells that express inhibitory KIRs for which the corresponding KIR–ligand is missing on autologous tissue, and thus will not be inhibited through KIR–ligand recognition. In some settings where an anticancer immunotherapeutic effect is likely mediated by NK cells, individuals with a KIR–ligand missing genotype have shown improved clinical outcome compared to individuals with an “all KIR–ligands present” genotype. In addition, patients receiving hematopoietic stem cell transplants for leukemia may do better if their donor has more activating KIR genes (i.e., KIR haplotype-B). In a recent multi-institution clinical trial of patients with metastatic renal cell carcinoma receiving high-dose IL2 (HD-IL2), 25 % of patients showed a complete or partial tumor response to this therapy. We genotyped KIR and KIR–ligand genes for these patients (n = 107) and tested whether KIR/KIR–ligand genotypes correlated with patient clinical outcomes. In these analyses, we did not find any significant association of KIR/KIR–ligand genotype (either KIR–ligand missing or the presence of KIR haplotype-B) with patient outcome in response to the HD-IL2 therapy.

from #Cancer-Sfakianakis via simeraentaxei on Inoreader http://ift.tt/2dy9nmH
via IFTTT Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174

Killer immunoglobulin-like receptor (KIR) and KIR–ligand genotype do not correlate with clinical outcome of renal cell carcinoma patients receiving high-dose IL2

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