Urosevic Mirjana, Braun Bettina, Willers Jörg, Burg Günter, Dummer Reinhard
Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
Exp Dermatol. 2005 Jul;14(7):491-7. doi: 10.1111/j.0906-6705.2005.00305.x.
The efficiency of melanoma immunotherapy appears to depend on both melanoma- and immune system-specific factors. Melanoma-specific factors include melanoma-associated antigen (MAA) expression as well as HLA class I molecule expression. We investigated the expression of five MAA - Melan-A/MART-1, tyrosinase, gp100, MAGE-1 and MAGE-3 - by means of FACS analysis in 50 melanoma cell cultures and compared them to the cultures of human foreskin-derived melanocytes and melanoma cell line UKRV-Mel2. Melan-A, tyrosinase and gp100 expression was frequently reduced in melanoma cell cultures, compared to that in foreskin melanocytes, whereas MAGE-1 and MAGE-3 expression showed variable degree of upregulation, compared to that in foreskin melanocytes. The expression of all tested MAA demonstrated high interindividual variability. We further show that cell cultures derived from the same tissue sample are oligoclonal in nature, by demonstrating the presence of up to three cell populations bearing distinct MAA profile. Analysing samples derived from the same patient but each at a different time point, we show that MAA expression profile changes over time either in positive (increase) or in negative (decrease) direction. Finally, we demonstrate that brain metastasis-derived cell cultures significantly overexpress Melan-A and MAGE-3, compared to primary tumours and other metastatic sites (P-value range: 0.05-0.001). Elucidation of the MAA expression patterns and the kinetics within the same patient as well as during the course of the disease may help improve current and develop new immunotherapeutic strategies.
黑色素瘤免疫疗法的疗效似乎取决于黑色素瘤特异性和免疫系统特异性因素。黑色素瘤特异性因素包括黑色素瘤相关抗原(MAA)表达以及HLA I类分子表达。我们通过流式细胞术分析,研究了50种黑色素瘤细胞培养物中5种MAA——Melan-A/MART-1、酪氨酸酶、gp100、MAGE-1和MAGE-3的表达情况,并将其与源自人包皮的黑色素细胞培养物以及黑色素瘤细胞系Ukrv-Mel2进行比较。与包皮黑色素细胞相比,黑色素瘤细胞培养物中Melan-A、酪氨酸酶和gp100的表达常常降低,而与包皮黑色素细胞相比,MAGE-1和MAGE-3的表达则呈现出不同程度的上调。所有检测的MAA的表达均表现出高度的个体间差异。我们进一步表明,源自同一组织样本的细胞培养物本质上是寡克隆的,通过证明存在多达三个具有不同MAA谱的细胞群体得以证实。分析来自同一患者但处于不同时间点的样本,我们发现MAA表达谱会随时间在正向(增加)或负向(减少)方向发生变化。最后,我们证明,与原发性肿瘤和其他转移部位相比,脑转移来源的细胞培养物中Melan-A和MAGE-3显著过表达(P值范围:0.05 - 0.001)。阐明同一患者体内以及疾病过程中的MAA表达模式和动力学,可能有助于改进当前的免疫治疗策略并开发新的策略。