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

Abstract

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.

Expression of RCAS1 and FasL in human trophoblasts and uterine glands during pregnancy: the possible role in immune privilege

“…Then tissue sections were incubated with the following monoclonal antibodies; L26 (CD20) monoclonal antibody (MAb) specific for B cells, anti‐CD3 MAb for T cells (Dakopatts, Copenhagen, Denmark), anti‐CD56 MAb for natural killer cells (T Cell Diagnostic, Cambridge, MA) and monoclonal antibody to Granzyme B (Pharmacell, Paris, France). An anti‐Fas ligand (FasL) antibody (Santa Cruz Biotechnology, Santa Cruz, CA) was also used for immunohistochemical staining, as described previously [20]. Biotinylated horse anti mouse IgG antibody (Vector, Burlingame, CA) was used as the second antibody.…”

Expression of intercellular adhesion molecule (ICAM)‐1 in adenoid cystic carcinoma of the head and neck

“…For the purposes of clinical correlation, the expression scores of ICAM‐1 were arbitrarily divided into two categories: high (positive cells > 40% of tumor cells) and low (positive cells ≤ 40%). TIA‐1 cells and CD68 cells were quantified by counting positively stained cells within a 0.25 × 0.25 mm grid (× 10 eyepiece with ×40 objective) in five fields of high concentration within the tumor 12,13 . An average of five counts gave a final mean value.…”

Tumor counterattack - concept and reality

“…Many CD95-resistant tumors express CD95L constitutively or after induction by chemotherapy ( [14,[23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39]; reviewed in [40]). Such tumor cells were shown to kill Jurkat or other CD95-positive apoptosis-sensitive cells in vivo.…”

“…A number of studies suggested that counterattack was also operative in vivo. Apoptosis of TIL has been found in situ within CD95L-expressing human melanoma [27], hepatocellular carcinoma [36], gastric adenocarcinoma [24] and lymphoepithelioma-like cancer of the stomach [28]. In esophageal cancer, the number of TIL was reduced concomitantly with increased TIL apoptosis within CD95L-expressing areas of the tumors [23].…”