In our previous study, the apoptotic cells were T-cells, especially CD8-positive cells rather than CD4-positive cells. Based on these findings, in Fas and perforin pathways, the CD8-positive cells were considered to be effector and target cells, while histiocytes could possibly be enhancers. As a result, both pathways seemed to induce an abundance of apoptosis and thus induce necrotizing lesions.

Interleukin-10 (IL-10) is an inhibitory cytokine produced by various cell types. It exhibits strong sequence homology to BCRF-1 (viral IL-10, vIL-10), an open reading frame in the Epstein-Barr-virus (EBV) genome. Using in situ hybridization (ISH), polymerase chain reaction (PCR) and immunohistochemistry, we checked 41 cases of nasopharyngeal carcinoma (NPC), to study the presence of EBV in the tumor cells, as well as to clarify the relationship between IL-10 expression of the tumor cells and the response of cytotoxic T cells. IL-10 expression was studied by immunohistochemistry; as a result, 29 of 41 cases expressed EBER-1 RNA of EBV by ISH. In addition, 19 of the 29 with EBV and 9 of 12 without EBV cases expressed IL-10 in the tumor cells. The number of cytotoxic T cells increased in the tumor tissue, and the increase in the intratumoral stroma was stronger than in the remaining normal epithelia. The number of cytotoxic T cells also significantly increased in the cases with EBV. On the other hand, in the IL-10-positive series, the number of cytotoxic T cells decreased significantly more than in IL-10-negative series. In view of the established inhibitory effects of IL-10, expression of IL-10 may therefore be one of the mechanisms for NPC cells as well as EBV to counter local immune defense. However, we could not conclude whether or not IL-10 expression was directly induced by EBV.

A low rate of apoptosis and high bcl-2 expression were recognized in EBV-positive gastric carcinomas, suggesting that bcl-2 protein is the main inhibitor of apoptosis in EBV-positive carcinomas. In addition, the low apoptotic and proliferative activities may reflect a low biological activity in EBV-positive gastric carcinomas.

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 ؉ G 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 F 0.05) and the number of apoptotic lymphocytes was significantly higher (p F 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 F 0.05). The number of apoptotic tumor cells in EBV ؉ tumors was significantly lower than in EBV ؊ cases (p F 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.

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. © 1999 Wiley‐Liss, Inc.