Synergistic effects of soluble PD-1 and IL-21 on antitumor immunity against H22 murine hepatocellular carcinoma.

Cancer immunotherapies are designed to elicit T-cell responses that inhibit tumor growth. Previous studies have demonstrated that interleukin 21 (IL-21) is a promising cytokine for cancer immunotherapy due to its ability to induce the immunity of T cells and natural killer cells, whereas blockade of the interaction of programmed death receptor-1 (PD-1) with its ligand (PD-L1) reduces peripheral tolerance. In the current study, we investigated IL-21 alone and in combination with soluble PD-1 (sPD-1) for the treatment of experimental H22 murine hepatocarcinoma. The naked plasmids pmIL-21 and/or psPD-1 were used for local gene transfer by injection. In these assays, sPD-1 combined with IL-21 was found to significantly inhibit the growth of the tumors in mice. Combined treatment with IL-21 and sPD-1 enhanced the antitumor immune response compared with that induced by IL-21 alone. Combined treatment was found to increase CTL cytotoxicity, increase the number of CTLs and NK cells in splenocytes, upregulate the cytokines IFN-γ and IL-2 and downregulate IL-10. Thus, immunotherapy with IL-21 in combination with sPD-1 was found to induce a more efficacious antitumor immune response, which may have potential clinical implications.