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 (Pc = 0.008) and in patients with sentinel lymph node (SLN)
melanoma metastasis (Pc = 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.