Augmentation of Antitumor Immune Effect on Mouse H22 Hepatocarcmoma by Recombinant Soluble PD-1 (sPD-1) Inhibitory Immunoreceptor

Objective: To evaluate the mechanism of the enhanced antitumor immune effect of the locally expressed soluble molecule sPD-1 on mouse H22 hepatoma. Methods: The mRNA expression level of PD-L1 and PD-L2, the lig ands of PD-1, were investigated in mouse H22 cells as well as H22 tumor tissues by using semi-quantitative RT-PCR method. The cytotoxicity assay in vitro was used to evaluate the lysis activity of HSP70-peptides complex-stimulated spleen cells on H22 cells when the tumor cells or spleen cells were pretreated with sPD-1. The antitumor effect of sPD-1 on H22 hepatoma was investigated by experiment in vivo after mice were inoculated with H22 tumor cells. Results: PD-L1 but not PD-L2 mRNA was expressed in H22 hepatoma cells. Both PD-L1 and PD-L2 mRNAs were expressed in tumor tissues of tumor-bearing mice and upregulated as compared with muscle tissues in normal mice. Blocking PD-Ls on either tumor cells or spleen cells by sPD-1 mediated enhanced lysis of H22 cells by HSP70-peptides complex-stimulated spleen cells. sPD 1 also mediated strong antitumor immune effects on mouse H22 tumor model in vivo. Conclusion: The results provide a novel antitumor method of expression of soluble receptor of PD-1 in tumor sites by local gene therapy, which could block the action of PD-Ls on both immune cells and H22 tumor cells, and then increase the antitumor immune activity.