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

BACKGROUND. The nonclassic human major histocompatibility complex class I a ntigens 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 mel anoma. METHODS, Soluble HLA-G was determined in serum samples of 190 melanoma pati ents with various stages of disease, with or without current therapy includ ing interferon (IFN)-alpha and different cytostatics in comparison to 126 h ealthy controls by using a two-step enzyme-linked immunoadsorbent assay. RESULTS, Serum sHLA-G was significantly (P < 0.0005) elevated in melanoma p atients (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). Univa riate analysis revealed a correlation of sHLA-G serum level with advanced s tages of disease (P < 0.001) and tumor load (P < 0.05). Patients undergoing immunotherapy with IFN-alpha (n = 31) showed an increased serum sHLA-G (me an +/- SEM = 62.05 +/- 7.58 ng/mL; P < 0.0005), whereas other treatment reg imens (n = 24) did not influence sHLA-G serum concentrations. Multivariate analysis revealed treatment with IFN-alpha as the only impact factor for el evated serum sHLA-G, lacking any correlation with stage of disease or tumor burden. Furthermore, IFN-ru was found to upregulate HLA-G cell surface exp ression on circulating monocytes. sHLA-G serum level was not associated wit h recurrence free or overall survival. CONCLUSIONS, This study shows increased sHLA-G serum concentrations in mela noma patients and additional enhancement upon treatment with IFN-ol. The le vel of serum sHLA-G, however, had no negative impact on patients' prognosis . (C) 2001 Americnn Cancer Society.