Human pancreatic cancer cells express non-functional Fas receptors and counterattack lymphocytes by expressing Fas ligand; a potential mechanism for immune escape

The aim of this study was to investigate the expression and functional stat us of Fas ligand (FasL) and its receptor (Fas) in human pancreatic cancers. Using RT-PCR: and Western blotting, Fas and FasL were expressed in seven s urgically resected pancreatic cancer specimens and five cell lines; Capan-1 , AsPC-1, BxPC-3, PANC-1, and MIA PaCa-2. In the resected specimens, pancre atic cancer cells induced apoptosis in the surrounding lymphoid cells. In c oculture experiments of pancreatic cancer and Jurkat T cells, 50% of Jurkat T cells underwent apoptosis after 2 days, however, almost all pancreatic c ancer cells remained viable. In addition, by testing Fas function using ant i-Fas antibody (CH11), all cell lines were resistant to Pas-mediated apopto sis except Capan-1 cells which showed sensitivity similar to that of Jurkat T cells. These results suggest that pancreatic cancer cells evade immune s urveillance by expression of FasL and non-functioning Fas that allow them t o 'counterattack' activated T-cells. These tumor escape mechanisms may cont ribute to the rapid fatal course of pancreatic cancer.