Abstract
Recent clinical investigations have demonstrated that T cell based immunotherapy of Malignant Pleural Mesothelioma (MPM) could represent an alternative to the other therapeutic strategies. However, its development suffers from the lack of identified tumour antigenic targets. Mucin1 (MUC1), which is expressed and recognized by cytotoxic T cells in numerous cancer types, is not investigated as a potential immune target in MPM. Thus, the objective of this study was to analyse MUC1 expression by MPM and to determine if this antigen can be the target of cytotoxic CD8+ T cells (CTL).
We first evaluated the expression and glycosylation of MUC1 by MPM cell lines using different MUC1 specific monoclonal antibodies. We then obtained a CTL clone specific of MUC1(950-958) peptide/HLA-A*0201 and studied its IFN-γ and cytotoxic response against MPM cell lines.
We found that all MPM cell lines expressed MUC1 protein at the cell surface with different glycosylation profiles. We also evidenced that HLA-A*0201+ MPM cell lines are recognized and lysed by a HLA-A*0201/MUC1(950-958) specific CTL clone independently of MUC1 glycosylation profile.
Thus, MUC1 expression and antigen presentation by MPM cells may represent an attractive target for immunotherapeutic treatment of MPM despite its hyperglycosylated profile.
- ERS