The combination of dendritic cells-cytotoxic T lymphocytes/cytokine-induced killer (DC-CTL/CIK) therapy exerts immune and clinical responses in patients with malignant tumors

Abstract

BACKGROUND: The clinical trials using immunotherapy have been performed for the treatment of variety of malignant tumors. However, large-scale meta-analysis of combined DC-CTL/CIK therapy on immune and clinical response in patients has not been well studied yet. The purpose of this study is to investigate the role of DC-CTL/CIK therapy and evaluate the changes of immune indicators and tumor serological markers both at an individual level and at a system level, which is an important basis for immunotherapy as well as prognosis estimation. METHODS: Three cohorts were designed to estimate therapeutic effects on patients with malignant tumors. Tumor serological markers were detected pre- and post-treatment by immunoradiometric methods using commercially available diagnostic kits. Lymphocyte subsets were identified by flow cytometry. The quality of life was assessed by EORTC QLQ-C30 questionnaire. RESULTS: In this study, we found out that Tregs was significantly reduced after transfusion of DC-CTL/CIK cells companied by decreasing serological tumor markers including AFP, CA199 and CA242 in primary liver cancer and CA724 in gastric cancer. A system-level analysis showed that lower percentages of Tregs were detected in patients with long-lasting courses of immunotherapy. Strikingly, a tumor progression indicator, myeloid-derived suppressor cells (MDSC), was dramatically decreased in patients after DC-CTL/CIK treatment. These results suggested that DC-CTL/CIK therapy improves immune functions and the quality of life post-treatment versus pre-therapy, indicating that DC-CTL/CIK therapy might block the deterioration of invasive cancers in these patients. CONCLUSIONS: This study demonstrated that DC-CTL/CIK therapy could reduce Tregs, MDSCs, and several crucial serological tumor markers in particular tumors, and improve the function of T cells immune systems and the quality of life in patients with malignant tumor.