Tao J, Li Y, Liu Y-Q, Li L, Liu J, Shen X, Shen G-X, Tu Y-T
Department of Dermatology, Affiliated Union Hospital, and Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Br J Dermatol. 2008 Jan;158(1):88-94. doi: 10.1111/j.1365-2133.2007.08294.x. Epub 2007 Nov 10.
Low expression of transporters associated with antigen processing (TAP) and human leucocyte antigen (HLA) class I, due to defects in the antigen presentation pathway, is frequently found in human tumours, including malignant melanoma (MM). This immune evasion renders many tumours unrecognizable by the host immune surveillance system and appears to play a role in the clinical course of the tumour, probably because it provides tumour cells with a mechanism to escape cytotoxic T-lymphocyte recognition and destruction. However, the histopathological significance of TAP and HLA class I antigen defects in MM remains unclear.
To study the expression of TAP and HLA class I antigen in MM and the relationship between them. To investigate the correlation between histopathological characteristics and expression of these molecules in MM.
Tissue sections from 77 patients with MM and 20 with naevi were examined using immunohistochemistry and morphological quantitative analysis for protein expression of TAP1, TAP2 and HLA class I antigen.
Positive TAP1, TAP2 and HLA class I antigen immunostaining was observed in 23%, 12% and 64% of MM lesions, respectively, and the expression of HLA class I was positively correlated with that of TAP1 and TAP2. However, expression of these molecules was positive in all of the pigmented naevi lesions. Reduced TAP1 and TAP2 protein expression in melanoma lesions was significantly associated with invasive growth, Clark's level and tumour-infiltrating lymphocytes. Reduced HLA class I antigen protein expression was only associated with tumour-infiltrating lymphocytes.
Our data suggest that reduced TAP1, TAP2 and HLA class I antigen protein expression in MM may contribute to the immune escape phenotype of human melanoma cells, and the main cause of reduced HLA class I expression may be the decreased TAP1 and TAP2 levels.
由于抗原呈递途径存在缺陷，与抗原加工相关的转运体（TAP）和人类白细胞抗原（HLA）I类分子的低表达在包括恶性黑色素瘤（MM）在内的人类肿瘤中经常被发现。这种免疫逃逸使得许多肿瘤无法被宿主免疫监视系统识别，并且似乎在肿瘤的临床进程中发挥作用，这可能是因为它为肿瘤细胞提供了一种逃避细胞毒性T淋巴细胞识别和破坏的机制。然而，MM中TAP和HLA I类抗原缺陷的组织病理学意义仍不清楚。
研究MM中TAP和HLA I类抗原的表达及其相互关系。探讨MM的组织病理学特征与这些分子表达之间的相关性。
采用免疫组织化学和形态学定量分析方法，检测77例MM患者和20例痣患者的组织切片中TAP1、TAP2和HLA I类抗原的蛋白表达。
MM病变中TAP1、TAP2和HLA I类抗原免疫染色阳性率分别为23%、12%和64%，HLA I类分子的表达与TAP1和TAP2呈正相关。然而，所有色素痣病变中这些分子的表达均为阳性。黑色素瘤病变中TAP1和TAP2蛋白表达降低与侵袭性生长、克拉克分级和肿瘤浸润淋巴细胞显著相关。HLA I类抗原蛋白表达降低仅与肿瘤浸润淋巴细胞有关。
我们的数据表明，MM中TAP1、TAP2和HLA I类抗原蛋白表达降低可能导致人类黑色素瘤细胞的免疫逃逸表型，HLA I类表达降低的主要原因可能是TAP1和TAP2水平降低。
