Soluble human leukocyte antigen-G serum level is elevated in melanoma patients and is further increased by interferon-α immunotherapy

Abstract

BACKGROUND. The nonclassic human major histocompatibility complex class I antigens human leukocyte antigen (HLA)-G are proposed to protect tumor cells from natural killer cell lysis. In the current study, the authors measured soluble HLA-G molecules (sHLA-G) in serum from patients with malignant melanoma. METHODS. Soluble HLA-G was determined in serum samples of 190 melanoma patients with various stages of disease, with or without current therapy including interferon (IFN)-α and different cytostatics in comparison to 126 healthy controls by using a two-step enzyme-linked immunoadsorbent assay. RESULTS. Serum sHLA-G was significantly (P < 0.0005) elevated in melanoma patients (mean ± standard error of the mean [SEM] = 41.95 ± 2.15 ng/mL) compared with healthy controls (mean ± SEM = 22.92 ± 1.51 ng/mL). Univariate analysis revealed a correlation of sHLA-G serum level with advanced stages of disease (P < 0.001) and tumor load (P < 0.05). Patients undergoing immunotherapy with IFN-α (n = 31) showed an increased serum sHLA-G (mean ± SEM = 62.05 ± 7.58 ng/mL; P < 0.0005), whereas other treatment regimens (n = 24) did not influence sHLA-G serum concentrations. Multivariate analysis revealed treatment with IFN-α as the only impact factor for elevated serum sHLA-G, lacking any correlation with stage of disease or tumor burden. Furthermore, IFN-α was found to upregulate HLA-G cell surface expression on circulating monocytes, sHLA-G serum level was not associated with recurrence free or overall survival. CONCLUSIONS. This study shows increased sHLA-G serum concentrations in melanoma patients and additional enhancement upon treatment with IFN-α. The level of serum sHLA-G, however, had no negative impact on patients' prognosis. © 2001 American Cancer Society.