Publication: KIR gene variability in cutaneous malignant melanoma: influence of KIR2D/HLA-C pairings on disease susceptibility and prognosis
Authors
Campillo, José A. ; López Álvarez, M. Rocío ; Bolarín, José Miguel ; Heras, Beatriz de las ; Muro, Manuel ; Minguela, Alfredo ; Moya Quiles, María Rosa ; Blanco García, Rosa ; Martínez Banaclocha, Helios ; García Alonso, Ana M. ; Álvarez López, María Rocío ; Martínez Escribano, Jorge A. ; Legaz Pérez, Isabel
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Publisher
Springer
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DOI
https://doi.org/10.1007/s00251-013-0682-0
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info:eu-repo/semantics/article
Description
© Springer-Verlag Berlin Heidelberg 2013.This document is the Published version of a Published Work that appeared in final form in Immunogenetics. To access the final edited and published work see https://doi.org/10.1007/s00251-013-0682-0
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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Citation
Immunogenetics (2013) 65:333–343
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