PMID- 11466692 OWN - NLM STAT- MEDLINE DCOM- 20010809 LR - 20201215 IS - 0008-543X (Print) IS - 0008-543X (Linking) VI - 92 IP - 2 DP - 2001 Jul 15 TI - Soluble human leukocyte antigen--G serum level is elevated in melanoma patients and is further increased by interferon-alpha immunotherapy. PG - 369-76 AB - 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)-alpha 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-alpha (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-alpha as the only impact factor for elevated serum sHLA-G, lacking any correlation with stage of disease or tumor burden. Furthermore, IFN-alpha 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-alpha. The level of serum sHLA-G, however, had no negative impact on patients' prognosis. CI - Copyright 2001 American Cancer Society. FAU - Ugurel, S AU - Ugurel S AD - Department of Dermatology, The Saarland University Hospital, Homburg/Saar, Germany. FAU - Rebmann, V AU - Rebmann V FAU - Ferrone, S AU - Ferrone S FAU - Tilgen, W AU - Tilgen W FAU - Grosse-Wilde, H AU - Grosse-Wilde H FAU - Reinhold, U AU - Reinhold U LA - eng PT - Journal Article PL - United States TA - Cancer JT - Cancer JID - 0374236 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antineoplastic Agents) RN - 0 (Biomarkers) RN - 0 (HLA Antigens) RN - 0 (HLA-G Antigens) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (Interferon-alpha) SB - IM MH - Antibodies, Monoclonal MH - Antineoplastic Agents/*pharmacology/therapeutic use MH - Biomarkers/*analysis MH - Enzyme-Linked Immunosorbent Assay MH - Female MH - Flow Cytometry MH - HLA Antigens/*analysis/biosynthesis MH - HLA-G Antigens MH - Histocompatibility Antigens Class I/*analysis/biosynthesis MH - Humans MH - Interferon-alpha/*pharmacology/therapeutic use MH - Male MH - Melanoma/drug therapy/*immunology/pathology MH - Middle Aged MH - Prognosis MH - Prospective Studies MH - Skin Neoplasms/drug therapy/*immunology/pathology EDAT- 2001/07/24 10:00 MHDA- 2001/08/10 10:01 CRDT- 2001/07/24 10:00 PHST- 2001/07/24 10:00 [pubmed] PHST- 2001/08/10 10:01 [medline] PHST- 2001/07/24 10:00 [entrez] AID - 10.1002/1097-0142(20010715)92:2<369::AID-CNCR1332>3.0.CO;2-U [pii] AID - 10.1002/1097-0142(20010715)92:2<369::aid-cncr1332>3.0.co;2-u [doi] PST - ppublish SO - Cancer. 2001 Jul 15;92(2):369-76. doi: 10.1002/1097-0142(20010715)92:2<369::aid-cncr1332>3.0.co;2-u.