Comparative analysis of the in vivo expression of tyrosinase, MART-1/Melan-A, and gp100 in metastatic melanoma lesions: Implications for immunotherapy
Comparative analysis of the in vivo expression of tyrosinase, MART-1/Melan-A, and gp100 in metastatic melanoma lesions: Implications for immunotherapy
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DOI：
10.1097/00002371-199801000-00003
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发表时间：
1998-01-01
影响因子：
3.9
通讯作者：
Topalian, SL
中科院分区：
文献类型：
--
作者：
Cormier, JN;Abati, A;Topalian, SL
已经鉴定了多种人黑素瘤相关抗原（MAA），其可以以主要组织相容性复合物限制的方式被T淋巴细胞识别。其中，酪氨酸酶、MART-1/Melan-A和gp 100来源于未突变的黑素细胞谱系特异性抗原（Ag）。这些Ag可以被CD 8（+）T细胞识别，并且在酪氨酸酶的情况下，可以被CD 4（+）T细胞识别。MAA的原位表达可能是决定Ag特异性T细胞识别黑素瘤靶点的重要辅助因素。在这项研究中，我们研究了这些MAA的表达模式，使用免疫组化方法对30个转移性肿瘤存款来自25例。MAA的表达在30个标本中是异质性的，在单个病变中也是异质性的。值得注意的是，23%的检测样本未能表达gp 100蛋白，17%的样本没有检测到MART-1的表达。相反，所有病变表现出一定程度的酪氨酸酶表达，即使在gp 100和MART-1都检测不到的情况下。此外，60%的样本（30个样本中的18个）显示酪氨酸酶强阳性（>75%的细胞染色），而gp 100为40%，MART-1为36%。目前，许多针对黑色素瘤的实验性免疫疗法针对MAA酪氨酸酶、MART-1和gp 100。虽然T细胞识别所需的Ag阈值水平尚未确定，但高密度表达的肿瘤相关Ag（如酪氨酸酶）可能是未来免疫治疗试验的更好靶点。
A variety of human melanoma-associated antigens (MAA) have been identified that can be recognized by T lymphocytes in a major histocompatibility complex-restricted fashion. Among them, tyrosinase, MART-1/Melan- A, and gp100 are derived from nonmutated melanocyte lineage-specific antigens (Ag). These Ag can be recognized by CD8(+) and, in the case of tyrosinase, CD4(+) T cells. The in situ expression of MAA may be a significant cofactor in determining the recognition of melanoma targets by Ag-specific T cells. In this study, we examined the patterns of expression of these MAA using immunohistochemical methods on 30 metastatic tumor deposits derived from 25 patients. MAA expression was heterogeneous among the 30 specimens and also within individual lesions. Of note, 23% of the samples examined failed to express the gp100 protein, and 17% of samples had no detectable expression of MART-1. In contrast, all lesions demonstrated some degree of tyrosinase expression even in cases where both gp100 and MART-1 were not detectable. In addition, 60% of samples (18 of 30) showed strong positivity for tyrosinase (>75% of cells staining) compared with 40% for gp100 and 36% for MART-1. Currently, a number of experimental immunotherapies for melanoma are directed against the MAA tyrosinase, MART-1, and gp100. Although threshold levels of Ag required for T-cell recognition have not yet been defined, tumor-associated Ag expressed in high density, such as tyrosinase, may be better targets for future immunotherapy trials.