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

Hdl Handle:
http://hdl.handle.net/10147/209166
Title:
Expression of Fas ligand by human gastric adenocarcinomas: a potential mechanism of immune escape in stomach cancer.
Authors:
Bennett, M W; O'connell, J; O'sullivan, G C; Roche, D; Brady, C; Kelly, J; Collins, J K; Shanahan, F
Affiliation:
Department of Medicine, Cork University Hospital, National University of Ireland,, Cork, Ireland.
Citation:
Gut. 1999 Feb;44(2):156-62.
Journal:
Gut
Issue Date:
3-Feb-2012
URI:
http://hdl.handle.net/10147/209166
PubMed ID:
9895372
Abstract:
BACKGROUND: Despite 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. AIM: To ascertain if human gastric tumours express FasL in vivo, as a potential mediator of immune escape in stomach cancer. SPECIMENS: Thirty paraffin wax embedded human gastric adenocarcinomas. METHODS: FasL 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). RESULTS: Prevalent 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. CONCLUSIONS: Human gastric adenocarcinomas express the immune downregulatory molecule, FasL. The results suggest that FasL is a prevalent mediator of immune privilege in stomach cancer.
Language:
eng
MeSH:
Adenocarcinoma/*immunology/pathology; Antigens, CD95/genetics/*metabolism; Antigens, Neoplasm/genetics/*metabolism; Apoptosis; Fas Ligand Protein; Gene Expression; Humans; Immunoenzyme Techniques; In Situ Hybridization; Ligands; Membrane Glycoproteins/genetics/*metabolism; RNA, Messenger/genetics; RNA, Neoplasm/genetics; Stomach Neoplasms/*immunology/pathology; Tumor Escape/*immunology
ISSN:
0017-5749 (Print); 0017-5749 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorBennett, M Wen_GB
dc.contributor.authorO'connell, Jen_GB
dc.contributor.authorO'sullivan, G Cen_GB
dc.contributor.authorRoche, Den_GB
dc.contributor.authorBrady, Cen_GB
dc.contributor.authorKelly, Jen_GB
dc.contributor.authorCollins, J Ken_GB
dc.contributor.authorShanahan, Fen_GB
dc.date.accessioned2012-02-03T15:14:01Z-
dc.date.available2012-02-03T15:14:01Z-
dc.date.issued2012-02-03T15:14:01Z-
dc.identifier.citationGut. 1999 Feb;44(2):156-62.en_GB
dc.identifier.issn0017-5749 (Print)en_GB
dc.identifier.issn0017-5749 (Linking)en_GB
dc.identifier.pmid9895372en_GB
dc.identifier.urihttp://hdl.handle.net/10147/209166-
dc.description.abstractBACKGROUND: Despite 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. AIM: To ascertain if human gastric tumours express FasL in vivo, as a potential mediator of immune escape in stomach cancer. SPECIMENS: Thirty paraffin wax embedded human gastric adenocarcinomas. METHODS: FasL 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). RESULTS: Prevalent 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. CONCLUSIONS: Human gastric adenocarcinomas express the immune downregulatory molecule, FasL. The results suggest that FasL is a prevalent mediator of immune privilege in stomach cancer.en_GB
dc.language.isoengen_GB
dc.subject.meshAdenocarcinoma/*immunology/pathologyen_GB
dc.subject.meshAntigens, CD95/genetics/*metabolismen_GB
dc.subject.meshAntigens, Neoplasm/genetics/*metabolismen_GB
dc.subject.meshApoptosisen_GB
dc.subject.meshFas Ligand Proteinen_GB
dc.subject.meshGene Expressionen_GB
dc.subject.meshHumansen_GB
dc.subject.meshImmunoenzyme Techniquesen_GB
dc.subject.meshIn Situ Hybridizationen_GB
dc.subject.meshLigandsen_GB
dc.subject.meshMembrane Glycoproteins/genetics/*metabolismen_GB
dc.subject.meshRNA, Messenger/geneticsen_GB
dc.subject.meshRNA, Neoplasm/geneticsen_GB
dc.subject.meshStomach Neoplasms/*immunology/pathologyen_GB
dc.subject.meshTumor Escape/*immunologyen_GB
dc.titleExpression of Fas ligand by human gastric adenocarcinomas: a potential mechanism of immune escape in stomach cancer.en_GB
dc.contributor.departmentDepartment of Medicine, Cork University Hospital, National University of Ireland,, Cork, Ireland.en_GB
dc.identifier.journalGuten_GB
dc.description.provinceMunster-

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