Combined induction with anti-PD-1 and anti-CTLA-4 antibodies provides synergistic antitumor effects in DC-CIK cells in renal carcinoma cell lines.

Immune escape of cancer cells has become the main challenge in the immunocytotherapy field. In this study, we analyzed the cytotoxicity of DC-CIK cells induced by anti-PD-1 and anti-CTLA-4 antibodies in RCC cell lines. Flow cytometry analysis was performed to analyze the immune phenotypes of DC-CIK cells. Click-iT EdU assay was performed to analyze the proliferation of DC-CIK cells. ELISA analysis was performed to detect the expression of cytokines in DC-CIK cells. Compared with DC-CIK cells without any treatment, the growth inhibition rate was significantly higher in the other three groups. Moreover, combined induction with anti-PD-1 plus anti-CTLA-4 antibodies provides synergistic antitumor effects of DC-CIK cells in renal carcinoma cell lines. The combined treatment promoted DC-CIK cell proliferation and differentiation into CD3+CD56+ NKT cells and CD3+CD8+ CTL cells. Compared with the control group, combined treatment significantly up-regulated the secretion of immune-stimulatory cytokines, such as IFN-γ and TNF-α, and down-regulated the secretion of the immunosuppressive cytokine IL-10. Furthermore, the co-induction promoted the early activation of DC-CIK cells. These results indicated the co-induction with anti-PD-1 plus anti-CTLA-4 antibodies improved antitumor effects of DC-CIK cells by promoting proliferation, differentiation, and early activation and regulating the secretion of immune-stimulatory and suppressive cytokines in renal carcinoma cell lines. IJCEP