Wang Ying, Yang Xijing, Yu Yi, Xu Zenghui, Sun Yan, Liu Hui, Cheng Jingbo, Liu Min, Sha Bibo, Li Linfang, Ding Na, Li Zhong, Jin Huajun, Qian Qijun
Department of Gene and Viral Therapy Laboratory, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 200438, China.
Department of Life Science and Technology, Tongji University, Shanghai, 200092, China.
J Cancer. 2018 Jan 1;9(2):275-287. doi: 10.7150/jca.22176. eCollection 2018.
The aim of this study was to evaluate the clinical response of immunotherapy with dendritic cell-cytotoxic T lymphocytes (DC-CTLs) in patients with hepatocellular carcinoma (HCC). Sixty-eight patients with a confirmed diagnosis of HCC and who received follow-up until December 2015 were enrolled. We measured immune phenotypes of DCs and activated T cells using flow cytometry and clinical indexes using an electrochemiluminescence method. DCs exhibited up-regulation of the maturation markers CD83, CD80, CD11c, and CD86 on day8. Levels of IFN-γ and TNF-α were higher in the DCs pulsed with tumor-associated antigens (TAAs) than in DCs with a non-proliferative recombinant adenovirus. The percentage of regulatory T cells (Tregs) decreased in patients after DC-CTLs therapy. In addition, serum levels of AFP, AFP-L3, ALT, and CA19-9 were significantly reduced in these patients. Quality of life was improved, especially on physical functioning scales. Median overall survival (OS) and progression-free survival (PFS) were 8.2 months and 4.3 months, respectively, for the control group and 12.8 months and 9 months, respectively, for the DC-CTL group. Patients treated with DC-CTLs therapy showed a statistically significant PFS and OS curve (OS: p=0.016; PFS: p<0.0001). In addition, no serious adverse reactions were observed. This study indicated that Tregs, as well as serum levels of AFP, AFP-L3, ALT, and CA19-9, which were correlated with a poor prognosis, decreased after DC-CTL treatments. The OS, PFS and the quality of life of HCC patients partially improved.
本研究旨在评估树突状细胞-细胞毒性T淋巴细胞（DC-CTL）免疫疗法对肝细胞癌（HCC）患者的临床反应。纳入了68例确诊为HCC且随访至2015年12月的患者。我们使用流式细胞术测量DC和活化T细胞的免疫表型，并使用电化学发光法测量临床指标。DC在第8天表现出成熟标志物CD83、CD80、CD11c和CD86的上调。用肿瘤相关抗原（TAA）脉冲处理的DC中IFN-γ和TNF-α水平高于用非增殖性重组腺病毒处理的DC。DC-CTL治疗后患者体内调节性T细胞（Treg）的百分比降低。此外，这些患者的血清甲胎蛋白（AFP）、甲胎蛋白-L3（AFP-L3）、谷丙转氨酶（ALT）和糖类抗原19-9（CA19-9）水平显著降低。生活质量得到改善，尤其是在身体功能量表方面。对照组的中位总生存期（OS）和无进展生存期（PFS）分别为8.2个月和4.3个月，DC-CTL组分别为12.8个月和9个月。接受DC-CTL治疗的患者显示出具有统计学意义的PFS和OS曲线（OS：p=0.016；PFS：p<0.0001）。此外，未观察到严重不良反应。本研究表明，与预后不良相关的Treg以及血清AFP、AFP-L3、ALT和CA19-9水平在DC-CTL治疗后降低。HCC患者的OS、PFS及生活质量得到部分改善。
