Article Text
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.
- Fas ligand
- gastric cancer
- immune escape
- apoptosis
- tumour
- mRNA
Abbreviations
- FasL
- Fas ligand
- TUNEL
- terminal deoxynucleotidyl transferase mediated dUTP nick end labelling
- TdT
- terminal deoxynucleotidyl transferase
- PBS
- phosphate buffered saline
- SSC
- 1 ×
- 0.15 M NaCl/0.015 M sodium citrate
- TIL, tumour infiltrating lymphocyte
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Abbreviations
- FasL
- Fas ligand
- TUNEL
- terminal deoxynucleotidyl transferase mediated dUTP nick end labelling
- TdT
- terminal deoxynucleotidyl transferase
- PBS
- phosphate buffered saline
- SSC
- 1 ×
- 0.15 M NaCl/0.015 M sodium citrate
- TIL, tumour infiltrating lymphocyte