Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt.
Cancer Biology Department, National Cancer Institute (NCI), Cairo University, Cairo, Egypt.
J Hepatocell Carcinoma. 2014 Jun 9;1:55-63. doi: 10.2147/JHC.S56012. eCollection 2014.
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.
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.
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.
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.
为了改善肝细胞癌(HCC)的治疗效果,许多最近的治疗干预措施都是必要的,包括免疫疗法,这似乎提供了一种新的现实治疗方式。本研究旨在通过评估外周血和细针抽吸物中获得的淋巴细胞的 IFN-γ 水平和表型来探索 HCC 患者免疫治疗的优化。
将分离的淋巴细胞在白细胞介素(IL)-2、IL-4 和 IL-12 的存在下培养。酶联免疫吸附试验和流式细胞术技术分别用于评估人 IFN-γ 的产生和研究的 T 细胞亚群。
用 IL-2 加 IL-12 处理的外周血淋巴细胞和肿瘤浸润淋巴细胞的混合细胞群在其培养基中显示 IFN-γ 水平显著升高,CD4(+)CD25(+)调节性 T 细胞的百分比显著降低,CD8(+)细胞毒性 T 细胞的百分比无明显增加。同时,IL-2 加 IL-4 处理显示无显著作用。
我们的数据表明,IL-12 与 IL-2 一起导致 CD4(+)CD25(+)调节性 T 细胞的抑制和 IFN-γ 水平的升高,这在 HCC 患者的治疗中发挥了至关重要的免疫治疗作用。