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KIR gene variability in cutaneous malignant melanoma: influence of KIR2D/HLA-C pairings on disease susceptibility and prognosis

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Abstract

Natural killer and CD8+ T cells are believed to be involved in the immune protection against melanoma. Their function may be regulated by a group of receptors defined as killer immunoglobulin-like receptors (KIRs) and their cognate HLA class I ligands. In this study, we analyzed the influence of KIR genes and KIR/HLA-I combinations on melanoma susceptibility and/or prognosis in a Spanish Caucasian population. For this purpose, KIR genotyping by PCR-SSP and HLA-C genotyping by reverse PCR-SSO were performed in 187 melanoma patients and 200 matched controls. We found a significantly low frequency of KIR2DL3 in nodular melanoma (NM) patients (P = 0.001) and in ulcerated melanoma patients (P < 0.0001). Similarly, the KIR2DL3/C1 combination was significantly decreased in melanoma patients (P c = 0.008) and in patients with sentinel lymph node (SLN) melanoma metastasis (P c = 0.002). Multivariate logistic regression models showed that KIR2DL3 behaves as a protective marker for NM and ulcerated melanoma (P = 0.02, odds ratio (OR) = 0.14 and P = 0.04, OR = 0.28, respectively), whereas the KIR2DL3/C1 pair acts as a protective marker for melanoma (P = 0.017, OR = 0.54), particularly superficial spreading melanoma (P = 0.02, OR = 0.52), and SLN metastasis (P = 0.0004, OR = 0.14). In contrast, the KIR2DL3(−)/C1C2 genotype seems to be correlated with NM and ulceration. We also report that the KIR2DL1(+)/S1(−)/C2C2 genotype is associated with susceptibility to melanoma and SLN metastasis. Altogether, the study of KIR2D genes and HLA-C ligands may help in assessing cutaneous melanoma risk and prognosis.

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Acknowledgments

The authors wish to thank S. Soriano, M. López, J.M. Alemany, M.J. Sanchís, and M.C. García-Calatayud for their excellent technical assistance and the Immunology, Dermatology, and Pathology Services of the Virgen de la Arrixaca University Hospital in Murcia for their kind collaboration. This work was supported by project PI-11/02644 from Fondo de Investigación Sanitaria (FIS), Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo, by project 04487/GERM/06 from the Séneca Foundation, Consejería de Educación CCAA Murcia, and by the collaboration of Cajamurcia. Isabel Legaz and Mª Rocio López-Álvarez are postdoctoral researchers from the Spanish Health Ministry and Séneca Foundation, respectively.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Immunology Department, Virgen de la Arrixaca University Hospital, Ctra. Madrid-Cartagena, 30120, El Palmar, Murcia, Spain

    José A. Campillo, Isabel Legaz, M. Rocío López-Álvarez, José Miguel Bolarín, Beatriz Las Heras, Manuel Muro, Alfredo Minguela, María R. Moya-Quiles, Rosa Blanco-García, Helios Martínez-Banaclocha, Ana M. García-Alonso & M. Rocío Álvarez-López

  2. Dermatology Department, Virgen de la Arrixaca University Hospital, Murcia, Spain

    Jorge A. Martínez-Escribano

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  1. José A. Campillo
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  2. Isabel Legaz
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  3. M. Rocío López-Álvarez
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Correspondence to José A. Campillo.

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The contribution by José A Campillo and Isabel Legaz is equal and the order of authorship is arbitrary.

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Campillo, J.A., Legaz, I., López-Álvarez, M.R. et al. KIR gene variability in cutaneous malignant melanoma: influence of KIR2D/HLA-C pairings on disease susceptibility and prognosis. Immunogenetics 65, 333–343 (2013). https://doi.org/10.1007/s00251-013-0682-0

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