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
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.