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.
Kume
T
T
First Department of Pathology, School of Medicine, Fukuoka University, Fukuoka, Japan.
Oshima
K
K
Yamashita
Y
Y
Shirakusa
T
T
Kikuchi
M
M
D000368:Aged; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000473:pathology* / Q000601:surgery / Q000821:virology; D053222:Fas Ligand Protein; D005260:Female; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D006801:Humans; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D016753:Interleukin-10 / Q000032:analysis; D008207:Lymphatic Metastasis; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis* / Q000235:genetics; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics; D013274:Stomach Neoplasms / Q000276:immunology* / Q000473:pathology* / Q000601:surgery / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000473:pathology; D019014:fas Receptor / Q000276:immunology
C099537:Epstein-Barr virus encoded RNA 1; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D012367:RNA, Viral; D019014:fas Receptor; D016753:Interleukin-10