Fas (Apo-1/CD95) and Fas ligand interaction between gastric cancer cells and immune cells.

Abstract

It has been proposed that the expression of Fas ligand (Fas L) in tumors may play an important role in immune escape. This study was undertaken to test a 'counterattack' theory as a mechanism of immune escape in gastric carcinoma. Expression of Fas and Fas L was examined in the human gastric cancer cell lines using reverse transcription-polymerase chain reaction. Cytotoxicity was determined by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay. Apoptosis of target Jurkat cells was examined after coculture with the effector gastric cancer cells in vitro. Immunohistochemical staining was performed for the detection of Fas and FasL in tumor-infiltrating lymphocytes (TIL) and gastric cancer cells in vivo. Apoptosis was detected by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) method in vitro and in vivo. Fas and FasL mRNA were found to be differentially expressed in gastric cancer cell lines. The coculture experiment showed that apoptosis of Jurkat was induced by a FasL-overexpressing effector gastric cell SNU-484. In a Fas-expressing gastric cell SNU-638, Fas expression was upregulated by the treatment of gamma-interferon in a time- and concentration-dependent manner. SNU-638 treated with gamma-interferon was more sensitive to anti-Fas antibody-mediated cytotoxicity than was the control cell line, suggesting an increase of functional Fas in gastric cancer cells. The expression of FasL in gastric cancer cells and of Fas in apoptotic TIL was also detected in vivo. The data indicate that the FasL expression of gastric cancer cells supports a 'counterattack theory' in gastric cancer cells and that the upregulation of Fas by IFN-gamma in SNU-638 may accelerate the apoptosis pathway through the Fas and FasL interaction between gastric cancer cells and immune cells. This result is supported by the expression of FasL in gastric cancer cells and apoptotic TIL in vivo. It is implicated that the different biological behaviors of gastric cancer cells could be at least in part explained by Fas and FasL interaction with immune cells.