الفهرس | Only 14 pages are availabe for public view |
Abstract Tumor microenvironment in hepatocellular carcinoma (HCC) plays an important role in the establishment and progression of tumors through immunity and inflammation mediated by lymphocytes. Many recent therapeutic interventions are necessary to improve the treatment of HCC including immunotherapy, which seems to offer one of the new realistic therapeutic modalities. Several trials are nowadays performed for immune-restoration against the immune suppressive action of cancer cells. This study aims to investigate the optimization of immunotherapy for HCC patients by appraisal of both interferon gamma (IFN-γ) levels and phenotyping of lymphocytes obtained from heparinized peripheral blood (HPB) and fine-needle aspirates (FNA). Lymphocytes were isolated from FNA and HPB of 28 HCC patients at National Cancer Institute, Cairo, Egypt. Cells were cultured in the presence of interleukins IL-2, IL-4 and IL-12. Enzyme-linked immunosorbent assay (ELISA) and flow cytometric techniques were used for the assessment of human IFN-production in the culture supernatants and the studied T-cell sub-populations respectively. This study also included 10 healthy subjects as controls. Mixed cell populations of peripheral blood lymphocytes (PBLs) and tumor infiltrating lymphocytes (TILs) responded better than autologous PBLs to mixed stimulatory cytokines; where the subsequent addition of IL-12 to IL-2 showed a good enhancement in IFN- secretion, CD4+ & CD8+ cells productions and an inhibitory effect on CD4+CD25+ regulatory T-cells (Tregs). Meanwhile, IL-2 plus IL-4 treatment possessed non-significant effects. IFN- levels were directly correlated with CD8+ cells during the co-treatment of IL-2+IL-4 and directly correlated with cell count during the co-treatment of IL-2+IL-12. In Conclusion, IL-12 together with IL-2 caused a suppression of CD4+CD25+ Tregs and an elevation of IFN-γ levels which play a crucial role for a proper immunotherapy in the management of patients with HCC. It is recommended to evaluate this experiment using a mixed cell populations of TILs and PBLs in the presence of IL-2 and IL-12 treatment as a promising biotherapy against cancer cells. |