Expression of Fas ligand by human gastric adenocarcinomas: a potential mechanism of immune escape in stomach cancer

Background-Despite being immunogenic, gastric cancers overcome antitumour i mmune responses by mechanisms that have yet to be fully elucidated. Fas lig and (FasL) is a molecule that induces Fas receptor mediated apoptosis of ac tivated immunocytes, thereby mediating normal immune downregulatory roles i ncluding immune response termination, tolerance acquisition, and immune pri vilege. Colon cancer cell lines have previously been shown to express Fast and kill lymphoid cells by Fas mediated apoptosis in vitro. Many diverse tu mours have since been found to express Fast suggesting that a "Fas countera ttack" against antitumour immune effector cells may contribute to tumour im mune escape. Aim-To ascertain if human gastric tumours express Fast in vivo, as a potent ial mediator of immune escape in stomach cancer. Specimens-Thirty paraffin wax embedded human gastric adenocarcinomas. Methods-FasL protein was detected in gastric tumours using immunohistochemi stry; Fast mRNA was detected in the tumours using in situ hybridisation. Ce ll death was detected in situ in tumour infiltrating lymphocytes using term inal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL). Results-Prevalent expression of Fast was detected in all 30 resected gastri c adenocarcinomas examined. In the tumours, Fast protein and mRNA were co-l ocalised to neoplastic gastric epithelial cells, confirming expression by t he tumour cells. Fast expression was independent of tumour stage, suggestin g that it may be expressed throughout gastric cancer progression. TUNEL sta ining disclosed a high level of cell death among lymphocytes infiltrating F ast positive areas of tumour. Conclusions-Human gastric adenocarcinomas express the immune downregulatory molecule, Fast. The results suggest that Fast is a prevalent mediator of i mmune privilege in stomach cancer.