Effect of interleukin 12 gene therapy on microvessel density and microenvironment in a rabbit model of vx2 liver cancer

AIM: To evaluate the effect of interleukin-12 (IL-12) gene ther apyon microvessel density and microenvironment in a postchemoembolization VX2 liver cancer model, and to investigate its anti-tumor mechanism. METHODS: Rabbits with VX2 hepatic tumors were randomized into 4 groups, with eight rabbits in each group. Interventional procedure protocols were performed as follows: 0.9% saline solution (group 1, control), transcatheter arterial chemoembolization alone (group 2, lipiodol + mitomycin), intra-arterial IL-12 gene infusion (group 3, IL-12 gene therapy alone), and intraarterial IL-12 gene infusion in combination with chemoembolization (group 4, IL-12 plus chemoembolization). Fourteen days after therapy, tumor tissues of the sacrificed animals were explanted for immunohistochemistry to evaluate microvessel density, effector T cells (CD3⁺, CD4⁺, and CD8⁺) and regulatory T cells (FoxP3⁺). RESULTS: The microvessel density and FoxP3⁺ T cells in group 2 were significantly higher than those in group 1, but the differences in CD3⁺, CD4⁺, and CD8⁺ T cells between the two groups were not significant. The microvessel density in gene therapy groups (groups 3 and 4) were significantly lower, and CD3⁺, CD4⁺, and CD8⁺ T cells in these two groups were significantly higher than those in groups 1 and 2. The differences in CD3⁺, CD4⁺, and CD8⁺ T cells between the two gene therapy groups (groups 3 and 4) were not significant. The difference in FoxP3⁺ T cells was not significant between before and after IL-12 gene therapy. The differences in the level of FoxP3 were not significant between groups 3 and 1, as well as between groups 4 and 2. CONCLUSION: IL-12 gene therapy can inhibit angiogenesis and induce effector T cell (CD3⁺, CD4⁺, and CD8⁺) infiltration in the VX2 liver cancer model, but the efficacy appears to be limited by the regulatory T cells (FoxP3+) existing in the tumors and overexpressed after chemoembolization.