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 reticulum. 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 downregulation was significantly associated with
tumor progression. Whereas 100% of melanomata in situ and 96.2% of primary
melanomas with a Breslow index of <or=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.