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

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. Cancer 2001;92:369–76. © 2001 American Cancer Society. The concentration of soluble nonclassic human major histocompatibility complex class I antigens human leukocyte antigen–G, proposed to protect tumor cells from lysis by natural killer cells, is elevated in serum from melanoma patients compared with healthy controls and shows further increase under treatment of patients with interferon‐α.