Journal
CANCER IMMUNOLOGY IMMUNOTHERAPY
Volume 65, Issue 12, Pages 1523-1532Publisher
SPRINGER
DOI: 10.1007/s00262-016-1904-8
Keywords
Renal cell carcinoma; High-dose IL2; Killer immunoglobulin-like receptors; HLA; NK cells
Categories
Funding
- Hyundai Hope on Wheels Grant
- Midwest Athletes Against Childhood
- Stand Up 2 Cancer
- The St. Baldrick's Foundation
- American Association of Cancer Research
- University of Wisconsin-Madison Carbone Cancer Center
- NCI-Cytokine Working Group
- Public Health Service Grants from the National Cancer Institute [CA014520, CA021115, CA023318, CA066636, CA180820, CA180794, CA021076, CA180799, CA14958, CA180816, CA166105, CA197078]
- National Institutes of Health
- Department of Health and Human Services
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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.
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