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Impaired cytotoxic T lymphocyte inductivity by dendritic cells derived from patients with hepatitis C virus-positive hepatocellular carcinoma
Authors:Tomoyoshi Ohno  Noboru Hirashima  Etsuro Orito  Izumi Hasegawa  Kei Fujiwara  Kiyoaki Itoh  Atsushi Ozasa  Noboru Shinkai  Yasuhito Tanaka  Takanobu Kato  Ryuzo Ueda   Kenji Sakakibara
Affiliation:Department of Gastroenterology, Social Insurance Chukyo Hospital, Nagoya, Japan.
Abstract:
Aim: Peptide-based therapeutic vaccines are being developed. The aim of this study was to determine the feasibility of immunotherapy to hepatitis C virus (HCV)-positive hepatocellular carcinoma (HCC) by assessing the inductivity of peptide-specific cytotoxic T lymphocyte (CTL) by dendritic cells. Methods: The inductivity of CTL was characterized in six patients with HCV-positive HCC, and compared to seven healthy volunteers and six patients with chronic HCV hepatitis (control). Results: Peptide-specific CTL was comparably induced in controls, but not induced in any patients with HCC. To characterize this, the cytokine profile and the expression of surface molecules interacting between dendritic and T cells were evaluated. Among the cytokines, production of interferon (IFN)-gamma was found to be impaired and closely related to the results of CTL assays, while the expression of surface molecules showed no significant changes. Conclusions: In HCV-positive HCC patients, CTL inductivity by dendritic cells is impaired. This may be related to the impaired production of IFN-gamma.
Keywords:cytotoxic T lymphocyte    dendritic cells    hepatitis C virus    hepatocellular carcinoma
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