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

  1. Author:
    Wang, W.
    Erbe, A. K.
    Gallenberger, M.
    Kim, K.
    Carmichael, L.
    Hess, D.
    Mendonca, E. A.
    Song, Y.
    Hank, J. A.
    Cheng, S. C.
    Signoretti, S.
    Atkins, M.
    Carlson, A.
    Weiss, J. M.
    Mier, J.
    Panka, D.
    McDermott, D. F.
    Sondel, P. M.

  2. Author Address

    Department of Human Oncology, University of Wisconsin, 4159 WIMR Bldg. UW-Madison Campus, 1111 Highland Avenue, Madison, WI, 53705, USA. Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison, WI, USA. Department of Pediatrics, University of Wisconsin, Madison, WI, USA. Department of Biostatistics, Dana Farber Cancer Institute, Boston, MA, USA. Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA. The Cytokine Working Group, Rockville, MD, USA. Department of Medicine, Georgetown University, Washington, DC, USA. Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA, USA. NCI-Biologic Resources Branch, Frederick, MD, USA. Department of Human Oncology, University of Wisconsin, 4159 WIMR Bldg. UW-Madison Campus, 1111 Highland Avenue, Madison, WI, 53705, USA. pmsondel@humonc.wisc.edu. Department of Pediatrics, University of Wisconsin, Madison, WI, USA. pmsondel@humonc.wisc.edu.
    1. Year: 2016
    2. Date: Dec
    3. Epub Date: 2016-09-30
  2. Journal: Cancer immunology, immunotherapy : CII
    1. 65
    2. 12
    3. Pages: 1523-1532
  4. Type of Article: Article
  5. ISSN: 0340-7004
  1. 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.

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External Sources

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  2. DOI: 10.1007/s00262-016-1904-8
  3. PMID: 27695964
  4. PMCID: PMC5123674
  5. View record in Web of Science®
  6. WOS: 000387595000008

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