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The Influence of HLA and KIR Genes on Malignant Melanoma Development and Progression

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Archivum Immunologiae et Therapiae Experimentalis Aims and scope

Abstract

Many studies have described the role of killer immunoglobulin-like receptors (KIRs) and their cognate human leukocyte antigen (HLA) class I ligands in the immune protection against melanoma, but the effect of these markers on intra-individual variations in tumor development and progression has remained less clear. We performed KIR, HLA, and KIR/ligand analysis in 283 patients with malignant melanoma in order to evaluate their integrated influence on disease stage and progression. The patients were grouped according to AJCC staging, histological type of the primary tumor, progression, and survival rate. Analysis of HLA class I alleles revealed positive association of HLA-C*14 (Pc = 0.026, OR = 5.99) and negative association of HLA-C*02 (Pc = 0.026, OR = 0.43) with the disease. Decreased frequency of KIR2DS5 was observed in patients with rapid progression, as compared to those with slow progression. KIR BB genotype was prevalent in patients with metastasis (p = 0.004, OR = 0.025). KIR AA genotype was nearly twice as frequent in rapidly progressive cases, but without statistical relevance (p = 0.055, OR = 2.6). Significantly increased frequency of KIR2DL2 in the presence of C1 ligand (strong inhibition) was found in patients with AJCC III and IV, as compared to individuals with AJCC I stage (p = 0.045, OR = 1.93). In summary, our data imply that KIR/ligand gene content in patients could modulate the disease course towards unfavorable tumor behavior.

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Acknowledgements

This work was supported by the European Union Sixth Framework Program. It was a part of the ENACT European project, 2SHC-CT-2004-503306.

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Authors and Affiliations

  1. Department of Clinical Immunology with Stem Cell Bank, Alexandrovska University Hospital, Medical University, 1431, Sofia, Bulgaria

    Snezhina Mihailova Kandilarova, Anastassia Mihaylova, Milena Ivanova & Elissaveta Naumova

  2. Department of Dermatology, University Hospital Essen, Essen, Germany

    Annette Paschen & Dirk Schadendorf

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  1. Snezhina Mihailova Kandilarova
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  2. Annette Paschen
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  3. Anastassia Mihaylova
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  4. Milena Ivanova
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  5. Dirk Schadendorf
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  6. Elissaveta Naumova
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Correspondence to Snezhina Mihailova Kandilarova.

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The authors declare that there is no conflict of interest with regard to the work presented in this article.

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Kandilarova, S.M., Paschen, A., Mihaylova, A. et al. The Influence of HLA and KIR Genes on Malignant Melanoma Development and Progression. Arch. Immunol. Ther. Exp. 64 (Suppl 1), 73–81 (2016). https://doi.org/10.1007/s00005-016-0437-3

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  • DOI: https://doi.org/10.1007/s00005-016-0437-3

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