Absence of Bcl-2 and Fas/CD95/APO-1 predicts the response to immunotherapy in metastatic renal cell carcinoma
Absence of Bcl-2 and Fas/CD95/APO-1 predicts the response to immunotherapy in metastatic renal cell carcinoma
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DOI：
10.1038/sj.bjc.6603359
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发表时间：
2006-11-06
影响因子：
8.8
通讯作者：
Tomita, Y.
中科院分区：
文献类型：
--
作者：
Maruyama, R.;Yamana, K.;Tomita, Y.
免疫治疗是转移性肾细胞癌(RCC)的唯一有效治疗方法，但有效率仅为20%左右，且该治疗偶尔会伴随严重的不良反应。因此，需要选择对免疫治疗有高度敏感性的患者；然而，目前还没有一个有希望的分子标志物来预测肾癌对免疫治疗的反应。本研究旨在探讨细胞凋亡相关分子Bcl2和Fas以及细胞凋亡和增殖指数(AI、PI)在预测转移性肾细胞癌免疫治疗易感性中的作用。对40例转移性肾细胞癌根治性肾切除术后免疫治疗的肿瘤组织进行免疫组织化学检测。进展性疾病(PD)患者免疫治疗后存活率降低(P=0.006)。进展性疾病与原发灶PI增高相关(P=0.0087)。CR和PR组原发灶均为阴性，NC+PD组阳性率为40.6%(P=0.0373)。原发肿瘤均为Bcl2和Fas阴性的患者对免疫治疗的反应明显好于其余组(P=0.0022)。原发灶的Bcl2和Fas状态可作为选择转移性肾细胞癌患者进行免疫治疗的有用指标。
Immunotherapy is the only available treatment for metastatic renal cell cancer (RCC), but the response rate is only about 20% and the treatment is occasionally associated with severe adverse effects. Thus, the selection of patients with a high susceptibility to immunotherapy is needed; however, there is no promising molecular marker that can predict the response to immunotherapy for RCC. This study was carried out to elucidate the potential role of apoptosis-related molecules Bcl-2 and Fas, as well as apoptotic and proliferating indexes (AI, PI) as predictors of the susceptibility of metastatic RCC to immunotherapy. Immunohistochemical examination of tumour tissues from 40 patients with metastatic RCC undergoing postoperative immunotherapy after radical nephrectomy was performed. Patients with progressive disease (PD) after immunotherapy presented with decreased survival (P = 0.006). Progressive disease correlated with higher PI in the primary lesion (P = 0.0087). All primary tumours of CR or PR patients were negative for Bcl-2, whereas among NC+PD patients, 40.6% were positive for Bcl-2 (P = 0.0373). Patients in whom the primary tumours were both Bcl-2- and Fas-negative showed significantly better responses to immunotherapy in comparison with the remaining group (P = 0.0022). The Bcl-2 and Fas status of the primary lesion may become useful criteria for the selection of patients with metastatic RCC for immunotherapy.