Characterization of the molecular basis of
tumor recognition by T cells has shown that major histocompatibility complex (
MHC) class I molecules play a crucial role in presenting antigenic
peptide epitopes to cytotoxic T lymphocytes. MHC class Ia downregulation has been repeatedly described on
melanoma cells and is thought to be involved in the failure of the immune system to control
tumor progression. Proper assembly of
MHC class I molecules is dependent on several cofactors, e.g. the chaperones
calnexin and
calreticulin residing in the endoplasmic reticulum. Alterations in the expression of these chaperones may have important implications for MHC class I assembly,
peptide loading, and presentation on the
tumor cell surface and thus may contribute to the immune escape phenotype of
tumor cells. In the present study, we compared
melanoma lesions representing different stages of
tumor progression with regard to the expression of
calnexin and
calreticulin in
tumor cells by means of immunohistochemistry. Metastatic
melanoma lesions exhibited significant downregulation of
calnexin as compared to primary
melanoma lesions. In contrast, chaperone
calreticulin was expressed in
melanoma cells of primary as well as of metastatic lesions. Our data suggest that chaperone-downregulation, particularly
calnexin-downregulation, may contribute to the metastatic phenotype of
melanoma cells in vivo. Consistently, conserved chaperone expression in metastatic
melanoma lesions may be a useful criterion for selection of patients for treatment with T cell-based
immunotherapies.