Enhanced antitumor effects and improved immune status of dendritic cell and cytokine-induced killer cell infusion in advanced cancer patients

Abstract

Little progress has been made in the treatment of advanced cancer. Dendritic cells (DCs) plus cytokine-induced killer (CIK) cells have exhibited antitumor effects. Thus, the aim of the present study was to evaluate the clinical efficacy of DC-CIK cell treatment in patients with advanced cancer. A paired study including 57 patients treated with DC-CIK cells (DC-CIK group) and 33 patients treated with best supportive care alone (BSC group) was performed. The patients in the DC-CIK group were matched to those in the control group in terms of sex, age, tumor type and clinical stage. T-cell subsets were detected and overall survival (OS) was compared between the two groups. The results demonstrated that CD4⁺/CD25⁺ and CD8⁺/CD28^- subsets significantly decreased following DC-CIK immunotherapy (P<0.05). The CD3⁺, CD3⁺/CD8⁺, CD8⁺/CD28⁺ and CD3⁺/CD56⁺ T-cell subsets were significantly increased in the DC-CIK group compared with the BSC group, while the CD8⁺/CD28^- subset was significantly decreased. Univariate analysis demonstrated that a lower CD8⁺/CD28^- and a higher CD8⁺/CD28⁺ ratio were associated with prolonged OS in advanced cancer patients. In addition, DC-CIK treatment administration, age (>60 vs. <60 years), clinical stage and the frequency of CIK treatment significantly affected the OS of patients in the DC-CIK group. A CD8⁺/CD28^- ratio of <21.12 was found to decrease the hazard ratio (HR) of OS to 0.50 [95% confidence interval (CI): 0.29-0.87] and a CD8⁺/CD28⁺ ratio >9.04 was found to decrease the HR of OS to 0.45 (95% CI: 0.21-0.98). No serious side effects were observed in the DC-CIK group. Taken together, these data indicate that DC-CIK infusions were able to change the ratios of the T-cell subsets, which increased the T helper cell and cytotoxic T lymphocyte subsets, while it decreased regulatory T lymphocyte subsets. Thus, this method of immunotherapy was found to improve the imbalance in the immune system and prolong the OS in patients with advanced cancer.