Upper GI 05

Background: Adhesive interactions between pancreatic carcinoma and cytotoxic T cells may be crucial to an effective anti-cancer response. CD103 expressed on T lymphocytes is the only molecule that hetereotypically binds to E-cadherin, an epithelial cell adhesion molecule characteristically involved in homotypic epithelial cell–cell adhesion. The aim of this study was to show that loss of E-cadherin expression by pancreatic cancer cells, which is observed during the metastatic process, may occur as a result of the adhesion and cytolysis of cancer cells by T cells. Methods: E-cadherin negative pancreatic carcinoma cells were transfected with a plasmid vector coding for E-cadherin. Peripheral blood lymphocytes were then isolated and stimulated with transforming growth factor β1 (TGF-β1) to express CD103. The adhesion and cytotoxic potential of these lymphocytes against pancreatic cancer cell targets were assessed by flow cytometric adhesion and standard chromium release cytotoxicity assays. Results: CD103 expressing T lymphocytes showed significantly increased adhesion to E-cadherin transfected carcinoma cells (5.64:1) compared to wild-type pancreatic cells (1.47:1; P < 0.0001). Adhesion was significantly reduced in the presence of anti-CD103 blockade (2.25:1; P < 0.001). CD103 expressing T lymphocytes showed significantly increased cytolysis of E-cadherin transfected carcinoma cells compared to wild-type pancreatic cancer cells (18 per cent versus 39.3 per cent; P < 0.001). Cytolysis was significantly reduced in the presence of anti-CD103 blockade (17.8 per cent versus 38.5 per cent; P < 0.001). Conclusions: T-cell adhesion to and cytolysis of pancreatic carcinoma cells appear to be dependent on the CD103–E-cadherin interaction. Reduced or lost expression of E-cadherin in pancreatic carcinoma may therefore be part of the process whereby cancer cells escape T-cell destruction and may represent scope for immunotherapy.