Malignancies have developed several strategies to evade immune surveillance. We have investigated pancreatic cancer cell lines and pancreatic cancer surgical specimens to evaluate possibilities of tumor escape in the Fas system, and local immune suppression. Despite Fas expression the majority of cell lines was resistant to Fas-mediated apoptosis. The Fas-associated phosphatase-1 is a strong candidate to confer Fas resistance in pancreatic cancer cells. In addition, all investigated pancreatic cancer cell lines and cancer specimens expressed Fas ligand. Fas ligand was functional in cancer cell lines as shown by coculture assays of pancreatic cancer cell lines with Jurkat cells as targets. Additional local immune suppression was demonstrated by loss of T-cell receptor/CD3-zeta chain of pancreatic cancer infiltrating T-lymphocytes. We conclude that these tumor escape mechanisms may contribute to the poor prognosis of pancreatic cancer but also represent targets for new treatment modalities.