J Cancer 2018; 9(2):275-287. doi:10.7150/jca.22176
Immunotherapy of patient with hepatocellular carcinoma using cytotoxic T lymphocytes ex vivo activated with tumor antigen-pulsed dendritic cells
1. Department of Gene and Viral Therapy Laboratory, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 200438, China;
2. Department of Life Science and Technology, Tongji University, Shanghai, 200092, China;
3. Department of Biotherapy, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 200438, China;
4. Shanghai Cell Therapy Research Institute, Qianyang Road 75A, Shanghai, 201805, China;
5. Ningbo 5 th Hospital (Ningbo Cancer Hospital), Zhuangshi Avenue 1166, Ningbo, 315201, China.
* These authors contributed equally to this work
Wang Y, Yang X, Yu Y, Xu Z, Sun Y, Liu H, Cheng J, Liu M, Sha B, Li L, Ding N, Li Z, Jin H, Qian Q. Immunotherapy of patient with hepatocellular carcinoma using cytotoxic T lymphocytes ex vivo activated with tumor antigen-pulsed dendritic cells. J Cancer 2018; 9(2):275-287. doi:10.7150/jca.22176. Available from http://www.jcancer.org/v09p0275.htm
Purpose 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).
Method 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.
Results 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.
Conclusion 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.
Keywords: Dendritic cell-cytotoxic T lymphocyte, immunotherapy, Treg, quality of life.