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- Title
Killer immunoglobulin-like receptor (KIR) and KIR-ligand genotype do not correlate with clinical outcome of renal cell carcinoma patients receiving high-dose IL2.
- Authors
Wang, Wei; Erbe, Amy; Gallenberger, Mikayla; Kim, KyungMann; Carmichael, Lakeesha; Hess, Dustin; Mendonca, Eneida; Song, Yiqiang; Hank, Jacquelyn; Cheng, Su-Chun; Signoretti, Sabina; Atkins, Michael; Carlson, Alexander; Weiss, Jonathan; Mier, James; Panka, David; McDermott, David; Sondel, Paul
- 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.
- Subjects
IMMUNOGLOBULIN receptors; RENAL cell carcinoma; RENAL cancer; GENOTYPES; ALLELES
- Publication
Cancer Immunology, Immunotherapy, 2016, Vol 65, Issue 12, p1523
- ISSN
0340-7004
- Publication type
Article
- DOI
10.1007/s00262-016-1904-8