| Objective To investigate the synergistic effects of 4-1BBL in combination with sPD-1 in tumor therapy and the related immunological mechanisms. Methods BALB/c mice were inoculated intramuscularly (i.m.) with H22 tumor cells in the right hind thigh to establish the experimental hepatoma model. The eukaryotic expression plasmids of 4-1BBL and soluble PD-1 (sPD-1) were injected directly into the muscle for gene therapy. The weight of tumor was recorded. The expression of immunoregulatory genes in tumor microenvironment were detected. The change of lymphocyte in tumor tissue was detected too. Results Either transfection with 4-1BBL gene alone or sPD-1 gene alone could inhibit tumor growth to some extent, but the more significant therapeutic effect was obtained in the combinatorial treatment group, in which the tumor was conspicuously inhibited at the rate of 92.3%, compared with 78% in 4-1BBL group and 70.2% in sPD-1 group. The combination treatment resulted not only in the down-regulation of TGF-βand IL-10 genes, but also a much more significant up-regulation of IFN-γand IL-2 genes at the later phase of therapy. Conclusion The effect of immunotherapy on tumor can be augmented by the combination of 4-1BBL and sPD-1, which can improve the expression of the related immunoregulatory genes to establish a much better microenvironment in favor of antitumor immune response. |
