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葡萄膜黑色素瘤中转运体相关蛋白的表达

Transporter associated protein expression in uveal melanoma.

作者信息

Krishnakumar S, Lakshmi S A, Abhyankar D, Biswas J

机构信息

Department of Ocular Pathology, Vision Research Foundation, Sankara Nethralaya, 18 College Road, Chennai-600 006, Tamil Nadu, India.

出版信息

Br J Ophthalmol. 2004 Jul;88(7):925-8. doi: 10.1136/bjo.2003.018457.

Abstract

BACKGROUND/AIM: Transporter associated protein (TAP) is important for presenting peptides to major histocompatibility complex (MHC) class I molecules. Defects in TAP lead to decreased MHC class I expression. The immunoexpression of human leucocyte antigen (HLA) class I molecules and the TAP1 subunit were studied in primary uveal melanomas and correlated with the cell types and extrascleral extension.

METHODS

The HLA class I antigen and TAP1 subunit were analysed by immunoperoxidase staining with monoclonal antibodies on 45 primary uveal melanoma archival specimens. The tumours were divided into two groups-group A: tumours with no extrascleral extension; group B tumours with extrascleral extension/liver metastasis. Immunoanalysis was done by a semiquantitative method.

RESULTS

HLA class I antigen and TAP1 were decreased in 35 of 35 tumours with no extrascleral extension and positive in six of 10 tumours with liver metastasis. Decreased immunoexpression of HLA class I antigen and TAP1 in uveal melanomas with no extrascleral extension was significant (p<0.001). HLA class I antigen and TAP1 were negative in spindle cell melanomas (p<0.001).

CONCLUSIONS

HLA class I antigen and TAP1 expression were decreased in uveal melanomas with no extrascleral extension and in spindle cell melanomas. Decreased expression of TAP1 may lead to decreased expression of HLA class I antigen in uveal melanomas. This preliminary observation deserves further investigation, which may shed more light on the immune escape mechanisms of this tumour and thus enable novel therapeutic strategies.

摘要

背景/目的:转运相关蛋白(TAP)对于将肽段呈递给主要组织相容性复合体(MHC)I类分子至关重要。TAP缺陷会导致MHC I类分子表达降低。本研究对原发性葡萄膜黑色素瘤中人类白细胞抗原(HLA)I类分子和TAP1亚基的免疫表达进行了研究,并将其与细胞类型和巩膜外扩展情况相关联。

方法

采用单克隆抗体免疫过氧化物酶染色法,对45例原发性葡萄膜黑色素瘤存档标本进行HLA I类抗原和TAP1亚基分析。将肿瘤分为两组:A组为无巩膜外扩展的肿瘤;B组为有巩膜外扩展/肝转移的肿瘤。免疫分析采用半定量方法。

结果

35例无巩膜外扩展的肿瘤中,HLA I类抗原和TAP1均降低,10例有肝转移的肿瘤中有6例呈阳性。无巩膜外扩展的葡萄膜黑色素瘤中,HLA I类抗原和TAP1免疫表达降低具有显著性(p<0.001)。梭形细胞黑色素瘤中HLA I类抗原和TAP1均为阴性(p<0.001)。

结论

无巩膜外扩展的葡萄膜黑色素瘤和梭形细胞黑色素瘤中HLA I类抗原和TAP1表达降低。TAP1表达降低可能导致葡萄膜黑色素瘤中HLA I类抗原表达降低。这一初步观察结果值得进一步研究,这可能会更深入地揭示该肿瘤的免疫逃逸机制,从而制定新的治疗策略。

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Mechanisms of MHC class I--restricted antigen processing.MHC I类分子限制性抗原加工机制
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