Kageshita T, Hirai S, Ono T, Hicklin D J, Ferrone S
Department of Dermatology, Kumamoto University School of Medicine, Kumamoto, Japan.
Am J Pathol. 1999 Mar;154(3):745-54. doi: 10.1016/S0002-9440(10)65321-7.
Expression of the proteasome subunits LMP2 and LMP7, the MHC-encoded transporter subunits TAP1 and TAP2, and HLA Class I antigens was examined by immunoperoxidase staining in 10 nevi and 98 melanoma lesions (60 primary and 38 metastatic), because these molecules play an important role in the presentation of melanoma-associated peptide antigens to cytotoxic T cells. LMP2 was less frequently expressed than LMP7 in primary and metastatic melanoma lesions. TAP1, TAP2, and HLA Class I antigen expression was more frequently (P < 0.05) down-regulated in metastatic than in primary melanoma lesions and in nevi. A synchronous TAP1, TAP2, and HLA Class I antigen down-regulation was observed in 58% of primary and 52% of metastatic lesions. TAP and HLA Class I antigen down-regulation in primary lesions was significantly associated with lesion thickness, stage of disease, reduced time to disease progression, and reduced survival. These results suggest that TAP down-regulation plays a role in the clinical course of malignant melanoma, probably by providing melanoma cells with a mechanism to escape from cytotoxic T lymphocyte recognition during disease progression.
采用免疫过氧化物酶染色法，检测了10例痣和98例黑色素瘤病变（60例原发性和38例转移性）中蛋白酶体亚基LMP2和LMP7、MHC编码的转运蛋白亚基TAP1和TAP2以及HLA I类抗原的表达情况，因为这些分子在将黑色素瘤相关肽抗原呈递给细胞毒性T细胞的过程中发挥重要作用。在原发性和转移性黑色素瘤病变中，LMP2的表达频率低于LMP7。与原发性黑色素瘤病变和痣相比，转移性黑色素瘤病变中TAP1、TAP2和HLA I类抗原的表达下调更为频繁（P<0.05）。在58%的原发性病变和52%的转移性病变中观察到TAP1、TAP2和HLA I类抗原的同步下调。原发性病变中TAP和HLA I类抗原的下调与病变厚度、疾病分期、疾病进展时间缩短和生存率降低显著相关。这些结果表明，TAP下调在恶性黑色素瘤的临床病程中起作用，可能是通过为黑色素瘤细胞提供一种在疾病进展过程中逃避细胞毒性T淋巴细胞识别的机制。
