Expression data from UKRV-Mel-15a melanoma-derived clones resistant to cytolysis mediated by Melan-A/MART1 (26-35) cytotoxic T lymphocytes (CTL).

Efficient processing of target antigens by the ubiquitin-proteasome-system (UPS) is essential for treatment of cancers by T cell therapies. However, immune escape due to impaired expression of IFN--inducible components of the antigen presentation machinery and consequent inefficient processing of HLA-dependent tumor epitopes can be one important reason for failure of such therapies. Here, we show that repeated short-term co-cultures of Melan-A/MART-1 tumor antigen-expressing melanoma cells with Melan-A/MART-1 (26-35)-specific CTL led to the generation of clones resistant to CTL-mediated cell death. To determine which of the UPS components and its associated pathways was responsible for CTL escape; three UKRV-Mel-15a clones were subjected to microarray gene expression analysis.

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Ebstein F, Keller M, Paschen A, Walden P, Seeger M, Bürger E, Krüger E, Schadendorf D, Kloetzel PM, Seifert U