Yi Yongxiang, Han Jianbo, Fang Yuan, Liu Dongxiao, Wu Zuoyou, Wang Lili, Zhao Liang, Wei Qiang
Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Southeast University, Nanjing, Jiangsu 210003, P.R. China.
Department of Pathology, The Second Affiliated Hospital of Southeast University, Nanjing, Jiangsu 210003, P.R. China.
Mol Clin Oncol. 2016 Aug;5(2):337-341. doi: 10.3892/mco.2016.925. Epub 2016 Jun 10.
Sorafenib is the standard therapeutic strategy for recurrent hepatocellular carcinoma (HCC) following hepatectomy. However, only few patients truly benefit from this therapy. Thus, new strategies combined with sorafenib are urgently required. We herein present the case of a patient with hepatic and extrahepatic HCC recurrence following hepatectomy, who was treated by combined sorafenib, focused ultrasound knife and DRibbles-pulsed dendritic cell (DC) vaccine. Enzyme-Linked ImmunoSpot assay (ELISPOT) and intracellular staining (ICS) analysis were used to detect the secretion of interferon (IFN)-γ by T cells at different timepoints of the vaccine in order to evaluate the patient's specific T-cell response to SMMC-7721-derived DRibbles vaccine. The α-fetoprotein level decreased from 103,295 to 5 ng/ml and the patient displayed improved liver function, an Eastern Cooperative Oncology Group performance status score of 0, remission of liver metastases and disappearance of the lung metastases 8 months post-combination therapy. The computed tomography scan revealed the disappearance of liver metastases 2 years post-combination therapy. The ELISPOT data revealed a low antigen-specific T-cell response 4 weeks after the first vaccine cycle and the response decreased to nearly zero prior to the second cycle. However, high antigen-specific T-cell response was observed 2 weeks after the second vaccine cycle and did not decrease, even after 10 months, which was consistent with the result of the ICS analysis, which demonstrated that most of the secreted IFN-γ was produced by CD4 T cells, whereas a low CD8 T-cell response was observed (0.429 vs. 0.0665%, respectively). Our results demonstrated that antigen-specific T-cell response aimed to treat recurrent HCC may be induced through stimulation by the DC-DRibbles vaccine. The success of the treatment supports the combination of sorafenib, focused ultrasound knife and DC-DRibbles vaccine as a therapeutic strategy for patients with HCC recurrence following hepatectomy.
索拉非尼是肝切除术后复发性肝细胞癌（HCC）的标准治疗策略。然而，只有少数患者真正从这种治疗中获益。因此，迫切需要与索拉非尼联合的新策略。我们在此报告一例肝切除术后出现肝内和肝外HCC复发的患者，其接受了索拉非尼、聚焦超声刀和DRibbles脉冲树突状细胞（DC）疫苗联合治疗。采用酶联免疫斑点分析（ELISPOT）和细胞内染色（ICS）分析，在疫苗接种的不同时间点检测T细胞分泌干扰素（IFN）-γ，以评估患者对SMMC-7721衍生的DRibbles疫苗的特异性T细胞反应。联合治疗8个月后，甲胎蛋白水平从103295降至5 ng/ml，患者肝功能改善，东部肿瘤协作组体能状态评分为0，肝转移灶缓解，肺转移灶消失。计算机断层扫描显示联合治疗2年后肝转移灶消失。ELISPOT数据显示，第一个疫苗周期后4周抗原特异性T细胞反应较低，第二个周期前反应降至几乎为零。然而，第二个疫苗周期后2周观察到高抗原特异性T细胞反应，且即使在10个月后也未降低，这与ICS分析结果一致，ICS分析表明，分泌的IFN-γ大部分由CD4 T细胞产生，而CD8 T细胞反应较低（分别为0.429%和0.0665%）。我们的结果表明，通过DC-DRibbles疫苗刺激可诱导针对复发性HCC的抗原特异性T细胞反应。治疗的成功支持索拉非尼、聚焦超声刀和DC-DRibbles疫苗联合作为肝切除术后HCC复发患者的治疗策略。
