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

Zhaohu Yuan; Huikuan Yang; Yaming Wei

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

Int J Clin Exp Pathol. 2019 Jan 1;12(1):123-132. eCollection 2019.

Authors

Zhaohu Yuan^{1

2}, Huikuan Yang^{1

2}, Yaming Wei^{1

2}

Affiliations

¹ Department of Blood Transfusion, Guangzhou First People's Hospital, School of Medicine, South China University of Technology Guangzhou 510180, Guangdong, China.
² Guangdong Engineering Research Center of Precise Transfusion Guangzhou 510180, Guangdong, China.

PMID: 31933726
PMCID: PMC6944006

Abstract

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.

Keywords: Anti-PD-1 antibody; anti-CTLA-4 antibody; dendritic cell-activated CIK (DC-CIK) cells; renal carcinoma cell.