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

M W Bennett,^a J O'Connell,^a G C O'Sullivan,^b D Roche,^a C Brady,^a J Kelly,^a J K Collins,^a F Shanahan^a

^a Department of Medicine, Cork University Hospital, National University of Ireland, Cork, Ireland, ^b Department of Surgery, Mercy Hospital, National University of Ireland, Cork

Correspondence to: Professor F Shanahan, Department of Medicine, Clinical Sciences Building, University Hospital, Cork, Ireland.

Accepted for publication 19 August 1998

BackgroundDespite being immunogenic, gastric cancers overcome antitumour immune responses by mechanisms that have yet to be fully elucidated. Fas ligand (FasL) is a molecule that induces Fas receptor mediated apoptosis of activated immunocytes, thereby mediating normal immune downregulatory roles including immune response termination, tolerance acquisition, and immune privilege. Colon cancer cell lines have previously been shown to express FasL and kill lymphoid cells by Fas mediated apoptosis in vitro. Many diverse tumours have since been found to express FasL suggesting that a "Fas counterattack" against antitumour immune effector cells may contribute to tumour immune escape.
AimTo ascertain if human gastric tumours express FasL in vivo, as a potential mediator of immune escape in stomach cancer.
SpecimensThirty paraffin wax embedded human gastric adenocarcinomas.
MethodsFasL protein was detected in gastric tumours using immunohistochemistry; FasL mRNA was detected in the tumours using in situ hybridisation. Cell death was detected in situ in tumour infiltrating lymphocytes using terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL).
ResultsPrevalent expression of FasL was detected in all 30 resected gastric adenocarcinomas examined. In the tumours, FasL protein and mRNA were co-localised to neoplastic gastric epithelial cells, confirming expression by the tumour cells. FasL expression was independent of tumour stage, suggesting that it may be expressed throughout gastric cancer progression. TUNEL staining disclosed a high level of cell death among lymphocytes infiltrating FasL positive areas of tumour.
ConclusionsHuman gastric adenocarcinomas express the immune downregulatory molecule, FasL. The results suggest that FasL is a prevalent mediator of immune privilege in stomach cancer.
(GUT 1999;44:156-162)

Keywords: Fas ligand;  gastric cancer;  immune escape;  apoptosis;  tumour;  mRNA