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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-12

AUTHORS

Wei Wang, Amy K. Erbe, Mikayla Gallenberger, KyungMann Kim, Lakeesha Carmichael, Dustin Hess, Eneida A. Mendonca, Yiqiang Song, Jacquelyn A. Hank, Su-Chun Cheng, Sabina Signoretti, Michael Atkins, Alexander Carlson, Jonathan M. Weiss, James Mier, David Panka, David F. McDermott, Paul M. Sondel

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. More... »

PAGES

1523-1532

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00262-016-1904-8

DOI

http://dx.doi.org/10.1007/s00262-016-1904-8

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1006179640

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27695964


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