Downregulation of tapasin expression in progressive human malignant melanoma

被引:37
作者
Dissemond, J [1 ]
Kothen, T [1 ]
Mörs, J [1 ]
Weimann, TK [1 ]
Lindeke, A [1 ]
Goos, M [1 ]
Wagner, SN [1 ]
机构
[1] Univ Essen Gesamthsch, Sch Med, Dept Dermatol, D-45122 Essen, Germany
关键词
tapasin; MHC class I; melanoma; metastases;
D O I
10.1007/s00403-003-0393-8
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
Tumor cells with alterations in the MHC class I peptide-loading complex are unable to load peptide antigens onto MHC class I molecules. These alterations result in destabilization of MHC class I expression on the tumor cell surface and thus play a critical role in escape from immunological recognition by the acquired cellular immune system. By forming physical links between class I heavy chains and TAP molecules, a component of the class I peptide-loading complex, tapasin, plays an important role in the assembly of MHC class I molecules with peptides in the endoplasmic reticulurn. In the present study, we compared 104 human melanoma lesions representing different stages of tumor progression for their expression of tapasin in tumor cells by immunohistochemistry. Tapasin down-regulation was significantly associated with tumor progression. Whereas 100% of melanomata in situ and 96.2% of primary melanomas with a Breslow index of less than or equal to 0.75 mm showed strong expression of tapasin, significant downregulation of tapasin was observed in 25% of primary melanomas with a Breslow index >0.75 mm as well as in 21.1% metastatic melanoma lesions. The downregulation of tapasin in advanced stages of human melanoma may reflect the accumulation of alterations in the antigen-presenting/processing machinery associated with neoplastic progression. These alterations may lead to failure of the acquired cellular immune system to control progression and metastatic spread of melanoma cells in vivo, and thus contribute to the immune escape phenotype of human melanoma cells.
引用
收藏
页码:43 / 49
页数:7
相关论文
共 26 条
[1]  
Bennett EM, 1999, J IMMUNOL, V162, P5049
[2]   IMMUNOENZYMATIC LABELING OF MONOCLONAL-ANTIBODIES USING IMMUNE-COMPLEXES OF ALKALINE-PHOSPHATASE AND MONOCLONAL ANTI-ALKALINE PHOSPHATASE (APAAP COMPLEXES) [J].
CORDELL, JL ;
FALINI, B ;
ERBER, WN ;
GHOSH, AK ;
ABDULAZIZ, Z ;
MACDONALD, S ;
PULFORD, KAF ;
STEIN, H ;
MASON, DY .
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 1984, 32 (02) :219-229
[3]   The nature of the MHC class I peptide loading complex [J].
Cresswell, P ;
Bangia, N ;
Dick, T ;
Diedrich, G .
IMMUNOLOGICAL REVIEWS, 1999, 172 :21-28
[4]   HLA-B27 misfolding is associated with aberrant intermolecular disulfide bond formation (dimerization) in the endoplasmic reticulum [J].
Dangoria, NS ;
DeLay, ML ;
Kingsbury, DJ ;
Mear, JP ;
Uchanska-Ziegler, B ;
Ziegler, A ;
Colbert, RA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (26) :23459-23468
[5]   How does TAP associate with MHC class I molecules? [J].
Elliott, T .
IMMUNOLOGY TODAY, 1997, 18 (08) :375-379
[6]   LOSS OF HLA CLASS-I ANTIGENS BY MELANOMA-CELLS - MOLECULAR MECHANISMS, FUNCTIONAL-SIGNIFICANCE AND CLINICAL RELEVANCE [J].
FERRONE, S ;
MARINCOLA, FM .
IMMUNOLOGY TODAY, 1995, 16 (10) :487-494
[7]   Impaired immune responses and altered peptide repertoire in tapasin-deficient mice [J].
Garbi, N ;
Tan, P ;
Diehl, AD ;
Chambers, BJ ;
Ljunggren, HG ;
Momburg, F ;
Hämmerling, GJ .
NATURE IMMUNOLOGY, 2000, 1 (03) :234-238
[8]   Impaired assembly yet normal trafficking of MHC class I molecules in tapasin mutant mice [J].
Grandea, AG ;
Golovina, TN ;
Hamilton, SE ;
Sriram, V ;
Spies, T ;
Brutkiewicz, RR ;
Harty, JT ;
Eisenlohr, LC ;
Van Kaer, L .
IMMUNITY, 2000, 13 (02) :213-222
[9]  
Harris MR, 1998, J IMMUNOL, V160, P5404
[10]   Down-regulation of HLA class I antigen-processing molecules in malignant melanoma - Association with disease progression [J].
Kageshita, T ;
Hirai, S ;
Ono, T ;
Hicklin, DJ ;
Ferrone, S .
AMERICAN JOURNAL OF PATHOLOGY, 1999, 154 (03) :745-754