O'Connell J, O'Sullivan G C, Collins J K, Shanahan F
National University of Ireland, Cork, Ireland.
J Exp Med. 1996 Sep 1;184(3):1075-82. doi: 10.1084/jem.184.3.1075.
Tumors escape immunological rejection by a diversity of mechanisms. In this report, we demonstrate that the colon cancer cell SW620 expresses functional Fas ligand (FasL), the triggering agent of Fas receptor (FasR)-mediated apoptosis within the immune system. FasL mRNA and cell surface FasL were detected in SW620 cells using reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical staining, respectively. We show that SW620 kills Jurkat T cells in a Fas-mediated manner. FasR-specific antisense oligonucleotide treatment, which transiently inhibited FasR expression, completely protected Jurkat cells from killing by SW620. FasL-specific antisense oligonucleotide treatment of SW620 inhibited its Jurkat-killing activity. FasL has recently been established as a mediator of immune privilege in mouse retina and testis. Our finding that colon cancer cells express functional FasL suggests it may play an analogous role in bestowing immune privilege on human tumors. HT29 and SW620 colon cancer cells were found to express FasR mRNA and cell surface FasR using RT-PCR and immunofluorescence flow cytometry, respectively. However, neither of these cells underwent apoptosis after treatment by the anti-FasR agonistic monoclonal antibody CH11. Our results therefore suggest a Fas counterattack model for immune escape in colon cancer, whereby the cancer cells resist Fas-mediated T cell cytotoxicity but express functional FasL, an apoptotic death signal to which activated T cells are inherently sensitive.
肿瘤通过多种机制逃避免疫排斥。在本报告中，我们证明结肠癌细胞SW620表达功能性Fas配体（FasL），它是免疫系统中Fas受体（FasR）介导的细胞凋亡的触发因子。分别使用逆转录聚合酶链反应（RT-PCR）和免疫组织化学染色在SW620细胞中检测到FasL mRNA和细胞表面FasL。我们表明SW620以Fas介导的方式杀死Jurkat T细胞。FasR特异性反义寡核苷酸处理可短暂抑制FasR表达，从而完全保护Jurkat细胞免受SW620的杀伤。对SW620进行FasL特异性反义寡核苷酸处理可抑制其对Jurkat细胞的杀伤活性。FasL最近已被确定为小鼠视网膜和睾丸免疫赦免的介质。我们发现结肠癌细胞表达功能性FasL，这表明它可能在赋予人类肿瘤免疫赦免方面发挥类似作用。分别使用RT-PCR和免疫荧光流式细胞术发现HT29和SW620结肠癌细胞表达FasR mRNA和细胞表面FasR。然而，在用抗FasR激动性单克隆抗体CH11处理后，这些细胞均未发生凋亡。因此，我们的结果提示了结肠癌免疫逃逸的Fas反击模型，即癌细胞抵抗Fas介导的T细胞细胞毒性，但表达功能性FasL，而活化的T细胞对FasL这种凋亡死亡信号天生敏感。
