Fas (CD95/APO-1) and Fas ligand expression in normal pancreas and pancreatic tumors. Implications for immune privilege and immune escape

Abstract

Background: Fas (CD95/APO-1) and Fas ligand (FasL) play key roles in immunologic homeostasis and immune privilege and may regulate normal cell turnover. Earlier studies had suggested that FasL-positive pancreatic carcinoma cell lines can induce apoptosis in T cells, thereby evading host immune surveillance. In the current study the authors have characterized the expression of Fas and FasL in the normal pancreas and in pancreatic neoplasia.

Methods: Pancreatic resection specimens with ductal-type adenocarcinoma or intraductal dysplasia (n = 41), nonductal pancreatic neoplasms (n = 5), and chronic pancreatitis (n = 4) were examined for Fas and FasL expression by immunohistochemistry. The results in invasive adenocarcinoma were compared to those for benign ducts and intraductal dysplasia, and correlated with clinicopathologic features of the tumors and with patient survival.

Results: Fas was expressed in the normal pancreatic ducts and in intraductal dysplasia in a mixed membrane/cytoplasmic pattern. In all cases of invasive ductal-type adenocarcinoma, membranous Fas could not be detected; cytoplasmic Fas staining was reduced or completely lost. Loss of Fas expression in pancreatic ductal-type adenocarcinomas significantly correlated with poorer differentiation and extrapancreatic spread of the tumors and was associated with a shorter overall survival. FasL expression was present in the normal pancreatic ducts as well as in islet cells and was maintained in all pancreatic tumors.

Conclusions: These results implicate the Fas pathway in the regulation of physiologic cell turnover and immune privilege in the normal pancreas and indicate that loss of Fas expression is correlated with malignant transformation and biologic aggressiveness in pancreatic adenocarcinomas. This may represent a mechanism by which pancreatic tumor cells become resistant to apoptosis and escape immune surveillance in vivo.