Mizutani Y, Yoshida O, Bonavida B
Department of Urology, Faculty of Medicine, Kyoto University, Japan.
J Urol. 1998 Aug;160(2):571-6.
The interaction of Fas antigen (Fas) and Fas ligand plays an important role in cytotoxic T lymphocyte- and natural killer cell-mediated cytotoxicity against cancer cells. Circulating soluble Fas (sFas) antagonizes cell-surface Fas function and may interfere with immune surveillance against autologous tumors. This possibility was examined in patients with bladder cancer.
The levels of sFas in the serum of 173 patients with bladder cancer were determined by using an enzyme-linked immunosorbent assay. Cytotoxicity of anti-Fas monoclonal antibody was examined by a 1-day microculture tetrazolium dye assay. Anti-autologous tumor cytotoxic activity was determined by the 12-hour 51Cr release assay.
The mean serum level of sFas in patients with bladder cancer was threefold higher than the mean in normal donors. The patients were divided into 2 groups based on the level of sFas in the serum. Bladder cancer patients with low level of serum sFas (less than the mean value) had a higher disease-specific survival rate, when compared with those with high level of serum sFas (greater than the mean value) in the 5-year followup. There were no statistical differences in patients' age and sex, as well as histological stage and grade of bladder cancer between the patients with high and low levels of serum sFas. Furthermore, patients with Ta bladder cancer with a low level of serum sFas had a longer postoperative tumor-free interval than those with high level in the 5-year followup. Cytotoxic activity of peripheral blood lymphocytes against autologous tumor cells was examined in 25 patients. There was an inverse correlation between the level of serum sFas and anti-autologous tumor cytotoxicity.
The findings suggest that elevated levels of sFas in the serum might be associated with poor prognosis in patients with bladder cancer.
Fas抗原(Fas)与Fas配体的相互作用在细胞毒性T淋巴细胞和自然杀伤细胞介导的针对癌细胞的细胞毒性中起重要作用。循环可溶性Fas(sFas)可拮抗细胞表面Fas功能,并可能干扰对自体肿瘤的免疫监视。本研究在膀胱癌患者中检验了这种可能性。
采用酶联免疫吸附测定法测定173例膀胱癌患者血清中的sFas水平。通过1天微量培养四唑盐染料测定法检测抗Fas单克隆抗体的细胞毒性。通过12小时51Cr释放测定法测定抗自体肿瘤细胞毒性活性。
膀胱癌患者血清sFas的平均水平比正常供体的平均水平高3倍。根据血清中sFas水平将患者分为2组。在5年随访中,血清sFas水平低(低于平均值)的膀胱癌患者的疾病特异性生存率高于血清sFas水平高(高于平均值)的患者。血清sFas水平高和低的患者在年龄、性别以及膀胱癌的组织学分期和分级方面无统计学差异。此外,在5年随访中,血清sFas水平低的Ta期膀胱癌患者的术后无瘤间期比水平高的患者更长。对25例患者检测了外周血淋巴细胞对自体肿瘤细胞的细胞毒性活性。血清sFas水平与抗自体肿瘤细胞毒性之间呈负相关。
研究结果表明,血清中sFas水平升高可能与膀胱癌患者的预后不良有关。