Potential immunotherapeutic role of interleukin-2 and interleukin-12 combination in patients with hepatocellular carcinoma

Abstract

BACKGROUND Many recent therapeutic interventions are necessary to improve the treatment of hepatocellular carcinoma (HCC), including immunotherapy, which seems to offer one of the new realistic therapeutic modalities. This study aims to investigate the optimization of immunotherapy for HCC patients by appraisal of both interferon (IFN)-γ levels and phenotyping of lymphocytes obtained from peripheral blood and fine-needle aspirates. METHODS The isolated lymphocytes were cultured in the presence of interleukins (IL)-2, IL-4, and IL-12. Enzyme-linked immunosorbent assay and flow cytometric techniques were used for the assessment of human IFN-γ production and the studied T-cell subpopulations, respectively. RESULTS Mixed cell populations of peripheral blood lymphocytes and tumor infiltrating lymphocytes treated with IL-2 plus IL-12 showed a marked and significant elevation in IFN-γ levels in their culture media, a significant decrease in the percentage of cluster of differentiation (CD)4(+)CD25(+) regulatory T-cells, and a nonsignificant increase in the percentage of CD8(+) cytotoxic T-cells. Meanwhile, IL-2 plus IL-4 treatment demonstrated nonsignificant effects. CONCLUSION Our data suggested that IL-12 together with IL-2 caused a suppression of CD4(+)CD25(+) regulatory T-cells and an elevation of IFN-γ levels, which play a crucial immunotherapeutic role in the management of HCC patients.