Si Tongguo, Guo Zhi, Hao Xishan
Department of Interventional Treatment, Tianjin Medical University Cancer Hospital and Institution, Tianjin, PR China.
J Immunother. 2009 Jan;32(1):86-91. doi: 10.1097/CJI.0b013e31818df785.
A total of 12 patients with metastatic hormone refractory prostate cancer were treated by combining cryoablation and granulocyte macrophage colony-stimulating factor administration. Besides prostate-specific antigen (PSA) measurements, peripheral blood mononuclear cells were also obtained; the frequency of tumor-specific T cells was tested ex vivo in an interferon-gamma enzyme-linked immunospot assay after stimulating with autologous prostate cancer-derived protein lysates. To assess cytolytic activity, T cells were coincubated with human prostate cancer cells (LNCaP) or renal cancer cells (GRC-1), and release of cytosolic adenylate kinase was measured by a luciferase assay. The median PSA decline percentage was 69.4% (range: 30.5% to 92.5%) and the median time to the nadir PSA was 4 months after therapy (range: 3 to 6). The median time to disease progress was 18 months, and 1 patient obtained a 92.5% PSA decline and a greater than 50% reduction of lung disease and survived 31 months. Four or 8 weeks after treatment, the tumor-specific T-cell responses were increased in peripheral blood mononuclear cell. The cytolytic activity against LNCaP was also increased significantly whereas no response was found against GRC-1. It seemed that there was no direct correlation between the degree of T-cell response and decline in PSA. Combined cryoablation with granulocyte macrophage colony-stimulating factor treatment was suggested to be an alternative approach for metastatic hormone refractory prostate cancer and could induce tumor-specific immunologic response.
总共12例转移性激素难治性前列腺癌患者接受了冷冻消融术与粒细胞巨噬细胞集落刺激因子给药相结合的治疗。除了检测前列腺特异性抗原（PSA）外，还获取了外周血单核细胞；在用自体前列腺癌衍生的蛋白裂解物刺激后，通过干扰素-γ酶联免疫斑点试验在体外检测肿瘤特异性T细胞的频率。为了评估细胞溶解活性，将T细胞与人前列腺癌细胞（LNCaP）或肾癌细胞（GRC-1）共同孵育，并通过荧光素酶测定法测量细胞溶质腺苷酸激酶的释放。PSA下降百分比的中位数为69.4%（范围：30.5%至92.5%），PSA降至最低点的中位时间为治疗后4个月（范围：3至6个月）。疾病进展的中位时间为18个月，1例患者PSA下降了92.5%，肺部疾病减少了50%以上，存活了31个月。治疗后4周或8周，外周血单核细胞中的肿瘤特异性T细胞反应增强。对LNCaP的细胞溶解活性也显著增加，而对GRC-1未发现反应。T细胞反应程度与PSA下降之间似乎没有直接相关性。冷冻消融术与粒细胞巨噬细胞集落刺激因子联合治疗被认为是转移性激素难治性前列腺癌的一种替代方法，并且可以诱导肿瘤特异性免疫反应。
