title: Altered cytokine levels and increased CD4+CD57+ T cells in the peripheral blood of hepatitis C virus-related hepatocellular carcinoma patients.
abstract: 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)-γ was undetectable in the plasma of patients with tumors at any stage, whereas the plasma levels of tumor necrosis factor (TNF)-α, 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-γ-producing capability of PB was highest in stage I patients and gradually decreased with tumor progression. The IL-10-, IL-18- and IL-12-producing capabilities of PB increased from stage I to III. However, PB-TNF-α, 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+αβTCR+ 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+αβTCR+ cells (CD4+ T cells), but not that of CD4+CD57+ T cells to CD57+αβTCR+ cells (CD57+ T cells), showed a significant inverse correlation with PB-IFN-γ-producing capability. The present results suggest that an increase in CD4+CD57+ T cells controls the capability of PB to produce the anti-tumor cytokine IFN-γ and that PB-IFN-γ production is impaired with HCC tumor progression.
authors.affiliation: Second Department of Internal Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-0012, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Shiraki
authors.forename: Eiji
authors.initials: E
authors.lastname: Takayama
authors.forename: Hirohito
authors.initials: H
authors.lastname: Magari
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nakata
authors.forename: Takao
authors.initials: T
authors.lastname: Maekita
authors.forename: Shotaro
authors.initials: S
authors.lastname: Enomoto
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Mori
authors.forename: Naoki
authors.initials: N
authors.lastname: Shingaki
authors.forename: Kosaku
authors.initials: K
authors.lastname: Moribata
authors.forename: Hisanobu
authors.initials: H
authors.lastname: Deguchi
authors.forename: Kazuki
authors.initials: K
authors.lastname: Ueda
authors.forename: Izumi
authors.initials: I
authors.lastname: Inoue
authors.forename: Masako
authors.initials: M
authors.lastname: Mizuno-Kamiya
authors.forename: Koji
authors.initials: K
authors.lastname: Yashiro
authors.forename: Mikitaka
authors.initials: M
authors.lastname: Iguchi
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Tamai
authors.forename: Yasunaga
authors.initials: Y
authors.lastname: Kameyama
authors.forename: Jun
authors.initials: J
authors.lastname: Kato
authors.forename: Nobuo
authors.initials: N
authors.lastname: Kondoh
authors.forename: Masao
authors.initials: M
authors.lastname: Ichinose
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D018959:CD57 Antigens / Q000096:biosynthesis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000821:virology; D002469:Cell Separation; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D016174:Hepacivirus / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism* / Q000821:virology; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018959:CD57 Antigens; D016207:Cytokines; D020382:Interleukin-18; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma