Altered cytokine levels and increased CD4(+)CD57(+) T cells in the peripheral blood of hepatitis C virus-related hepatocellular carcinoma patients

作者：Shiraki Tatsuya; Takayama Eiji^*; Magari Hirohito; Nakata Takahiro; Maekita Takao; Enomoto Shotaro; Mori Yoshiyuki; Shingaki Naoki; Moribata Kosaku; Deguchi Hisanobu; Ueda Kazuki; Inoue Izumi; Mizuno Kamiya Masako; Yashiro Koji; Iguchi Mikitaka; Tamai Hideyuki; Kameyama Yasunaga; Kato Jun; Kondoh Nobuo; Ichinose Masao

来源：Oncology Reports, 2011, 26(1): 201-208.

DOI：10.3892/or.2011.1258

• hepatocellular carcinoma
• hepatitis C virus
• tumor immunology
• peripheral blood lymphocyte
• cytokine-producing capability

Although CD57(+) lymphocytes are closely correlated with prognosis in various cancers, the role of subsets of CD57(+) cells in hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) is unclear. In the present study, peripheral blood (PB) from HCV-related HCC patients was analyzed. Plasma cytokine levels and in vitro cytokine-producing capabilities were analyzed with enzyme-linked immunosorbent assays, and CD57(+) cell subsets were studied using a multi-color FACS system. Interferon (IFN)-gamma was undetectable in the plasma of patients with tumors at any stage, whereas the plasma levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-10 and IL-18, but not that of IL-12, were significantly higher in stage IV patients compared to patients with earlier-stage tumors. In contrast, the IFN-gamma-producing capability of PB was highest in stage I patients and gradually decreased with tumor progression. The IL-10-, IL-18- and IL-12-proclucing capabilities of PB increased from stage I to III. However, PB-TNF-alpha, IL-10- and IL-18-producing capabilities were reduced in stage IV patients, probably due to repeated anti-cancer treatments. The percentage of CD4(+)CD57(+)alpha beta TCR+ cells (CD4(+)CD57(+) T cells) in peripheral blood lymphocytes (PBLs) increased with tumor progression. Moreover, the percentage of CD4(+)CD57(+) T cells in PBLs and the ratio of CD4(+)CD57(+) T cells to CD4(+)alpha beta TCR+ cells (CD4(+) T cells), but not that of CD4(+)CD57(+) T cells to CD57(+)alpha beta TCR+ cells (CD57(+) T cells), showed a significant inverse correlation with PB-IFN-gamma-producing capability. The present results suggest that an increase in CD4(+)CD57(+) T cells controls the capability of PB to produce the antitumor cytokine IFN-gamma and that PB-IFN-gamma production is impaired with HCC tumor progression.

• 出版日期2011-7