Kume T, Oshima K, Yamashita Y, Shirakusa T, Kikuchi M
First Department of Pathology, School of Medicine, Fukuoka University, Fukuoka, Japan.
Int J Cancer. 1999 Aug 20;84(4):339-43. doi: 10.1002/(sici)1097-0215(19990820)84:4<339::aid-ijc1>3.0.co;2-2.
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.
Fas/ Fas配体（Fas-L）系统参与细胞凋亡的诱导并介导T细胞的细胞毒性。为了解肿瘤细胞的免疫逃逸机制，我们对30例胃淋巴上皮瘤样癌（LECS）中的Fas/ Fas-L系统和细胞毒性T淋巴细胞（CTL）进行了研究。30例LECS中有15例检测到爱泼斯坦-巴尔病毒（EBV）。通过免疫组织化学染色检测肿瘤细胞中Fas和Fas-L的表达，以及淋巴细胞中TIA-1、CD4、CD8和CD56的表达。采用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法（TUNEL）检测肿瘤细胞和淋巴细胞的凋亡情况。分别在10例和17例LECS的肿瘤细胞中检测到Fas和Fas-L的表达。CTL主要由CD8组成（CD8(+) > CD4(+)），而仅在4例中检测到自然杀伤（NK）细胞。在Fas-L阳性肿瘤中，TIA-1阳性淋巴细胞计数显著低于Fas-L阴性病例（p < 0.05），凋亡淋巴细胞数量显著高于Fas-L阴性病例（p < 0.05）。EBV(+)病例中TIA-1阳性淋巴细胞数量显著高于EBV(-)肿瘤（p < 0.05）。EBV(+)肿瘤中凋亡肿瘤细胞数量显著低于EBV(-)病例（p < 0.01）。我们的结果表明，在LECS中，表达Fas-L的肿瘤细胞可能通过Fas/ Fas-L系统杀伤淋巴细胞来逃避免疫攻击。然而，在EBV(+) LECS肿瘤中，我们的结果表明大量CTL与凋亡肿瘤细胞数量减少有关。我们的研究结果表明，Fas/ Fas-L系统在EBV(+)肿瘤的肿瘤细胞免疫逃逸中起作用。《国际癌症杂志（肿瘤预测）》84:339 - 343，1999年。
