Relationship between Fas-ligand expression on carcinoma cell and cytotoxic T-lymphocyte response in lymphoepithelioma-like cancer of the stomach.

The Fas/Fas-ligand (Fas-L) system is involved in the induction of apoptosis and mediates T-cell cytotoxicity. We investigated the Fas/Fas-L system and cytotoxic T lymphocytes (CTLs) in 30 lymphoepithelioma-like cancer of the stomach (LECS) in order to understand the immune evasion of the tumor cells. Epstein-Barr virus (EBV) was detected in 15 cases in 30 LECSs. The expressions of Fas and Fas-L in tumor cells, and TIA-1, CD4, CD8 and CD56 in lymphocytes were examined by immunohistochemical staining. Apoptosis of tumor cells and lymphocytes was detected by the terminal deoxynucleotidyl-mediated dUTP-nick end labeling method (TUNEL). Expression of Fas and Fas-L was detected in tumor cells in 10 and 17 LECS, respectively. CTL consisted predominantly of CD8 (CD8(+) > CD4(+)), whereas natural killer (NK) cells were detected in 4 cases only. In Fas-L-positive tumors, the TIA-1-positive lymphocyte count was significantly lower (p < 0.05) and the number of apoptotic lymphocytes was significantly higher (p < 0.05) than in Fas-L-negative cases. The number of TIA-1-positive lymphocytes in EBV(+) cases was significantly higher than that in the EBV(-) tumors (p < 0.05). The number of apoptotic tumor cells in EBV(+) tumors was significantly lower than in EBV(-) cases (p < 0.01). Our results suggest that in LECS, tumor cells expressing Fas-L may evade the immune attack by killing lymphocytes through the Fas/Fas-L system. However, in EBV(+) LECS tumors, our results indicate that a high number of CTL is associated with a reduction in the number of apoptotic tumor cells. Our findings indicate that the Fas/Fas-L system plays a role in immune evasion of tumor cells in EBV(+) tumors. Int. J. Cancer (Pred. Oncol.) 84:339-343, 1999. Copyright 1999 Wiley-Liss, Inc.