2007 Fiscal Year Final Research Report Summary
Distinct responses of two hepatocellular carcinoma cell lines of a similar origin to immunotherapies targeting regulatory or effector T cells
| Project/Area Number |
18590739
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Nagasaki University |
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Principal Investigator |
NAKAO Kazuhiko Nagasaki University, Graduate School of Biomedical Sciences, Associate Professor (00264218)
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| Co-Investigator(Kenkyū-buntansha) |
NAGAYAMA Yuji Nagasaki University, Graduate School of Biomedical Sciences, Professor (30274632)
ICHIKAWA Tatsuki Nagasaki University, Hospital of Medicine and Dentistry, Assistant Professor (80346949)
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| Project Period (FY) |
2006 – 2007
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| Keywords | regulatory T cells(Treg) / effector T cells(Teff) / hepatoma / PC61 / cyclophosphamide / GITRL |
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| Research Abstract |
Balance between effector T cells (Teff)and regulatory T cells (Treg)appears to be very crucial for effective anti-tumor immunotherapy. The therapeutic efficacies of enhancement of Teff and suppression of Treg were compared between two murine hepatoma cell lines of a similar origin, MH129 and MH134. Enhancement of Teff was achieved by infection of tumor cells with adenovirus expressing glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR), and suppression of Treg, by depletion of CD4+CD25+ naturally occurring Treg by administration of anti-CD25 monoclonal antibody (PC61)or low-dose cyclophosphamide. Our data show that MH129 cells were susceptible to Treg depletion but resistant to GITR expression, and vice versa for MH134 cells. Thus, in MH129 cells, injection of PC61 prior to or after tumor cell inoculation completely or partially, respectively, eradicated tumor growth. Low-dose cyclophosphamide administered after tumor cell inoculation also delayed tumor growth.
… More
However, GTTR expression either in vitroor in vivo exhibited little effect. In contrast, in MH134 cells, PC61 induced partial tumor growth delay only when injected prior to tumor cell inoculation, and low-dose cyclophosphamide showed no effect, but GTTR, particularly when administered in vitro, inhibited tumor growth. An additive effect of PC61 and GITR was observed only in MH134 cells. The ratios of peripheral CD4+CD25+ CD4+ T cells remained unaltered during the experimental course in both tumor models. From these results we speculate that this different sensitivity may be due to a difference in relative induction levels of Teff versus Treg, not due to different immunogenicity or different kinetics of peripheral Treg, between the two tumor models. Future studies identifying antigen (s) or epitope (s) specific for Teff and Treg in these tumor cell lines are necessary as analysis of the immune response to such antigen (s) or epitope (s) may in general help predict the relative efficacy of different immunotherapies against distinct tumors. Less
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[Journal Article] Abrogation of constitutive STAT3 activity sensitizes human hepatoma cells to TRAIL-mediated apoptosis2007
Author(s)
Mariko, Kusaba, Kazuhiko, Nakao, Takashi, Goto, Disuke, Nishimura, Hiroshi Kawashimo, Hidetaka, Shibata, Yasuhide, Motoyoshi, Naota, Taura, Tatsuki, Ichikawa, Keisuke, Hamasaki, Katsumi, Eguchi
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Journal Title
Journal of Hepatology 47(4)
Pages: 546-555
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Distinct responses of two hepatocellular carcinoma cell lines of a similar origin to immunotherapies targeting regulatory or effector T cells2007
Author(s)
Yuji, Nagayama, Wataru, Hase, Yasuhide, Motoyoshi, Ohki, Saitoh, Rintaroh, Sogawa, Kazuhiko, Nakao
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Journal Title
Oncology Reports 17(5)
Pages: 1269-1273
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Polymorphisms of interleukin-1β in Japanese patients with hepatitis B virus infection2007
Author(s)
Kiyoshi, Migita, Yumi, Maeda, Seigo, Abiru, Minoru, Nakamura, Atsushi, Komori, Seiji, Miyazoe, Kazuhiko, Nakao, Hiroshi, Yatsuhashi, Katsumi, Eguchi, Hiromi, Ishibashi
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Journal Title
Journal of Hepatology 46(3)
Pages: 381-386
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Role of growth hormone, insulin-like growth factor 1 and insulin-like growth factor-binding protein 3 in development of non-alcoholic fatty liver disease2007
Author(s)
Tatsuki, Ichikawa, Kazuhiko, Nakao, Keisuke, Hamasaki, Ryuji, Furukawa, Shotarou Tsuruta, Yasuo, Ueda, Naota, Taura, Hidetaka, Shibata, Masumi, Fujimoto, Kan, Toriyama, Katsumi, Eguchi
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Journal Title
Hepatology International 1(2)
Pages: 287-294
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Different mechanisms for anti-tumor effects of low- and high-dose cyclophosphamide2006
Author(s)
Yasuhide, Motoyoshi, Kazuhisa, Kaminoda, Ohki, Saitoh, Keisuke, Hamasaki, Kazuhiko, Nakao, Nobuko, Ishii, Yuji, Nagayama, Katsumi, Eguchi
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Journal Title
Oncology Reports 16(1)
Pages: 141-146
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Survivin downregulation by siRNA sensitizes human hepatoma cells to TRAIL-induced apoptosis2006
Author(s)
Kazuhiko, Nakao, Keisuke, Hamasaki, Tatsuki, Ichikawa, Arima, Kazuhiko, Katsumi, Eguchi, Nobuko, Ishii
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Journal Title
Oncology Reports 16(2)
Pages: 389-392
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] DHMEQ, a novel NF-kB inhibitor, induces apoptosis and cell-cycle arrest in human hepatoma cells2006
Author(s)
Disuke, Nishimura, Hiroki, Ishikawa, Kojiro, Matsumoto, Hidetaka, Shibata, Yasuhide, Motoyoshi, Mariko, Fukuta, Hiroshi, Kawashimo, Takashi, Goto, Naota, Taura, Tatsuki, Ichikawa, Keisuke, Hamasaki, Kazuhiko, Nakao, Kazuo, Umezawa, Katsumi, Eguchi
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Journal Title
International Journal of Oncology 29(3)
Pages: 713-719
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Association between liver fibrosis and insulin sensitivity in chronic hepatitis C patients2006
Author(s)
Naota, Taura, Tatsuki, Ichikawa, Keisuke, Hamasaki, Kazuhiko, Nakao, Daisuke, Nishimura, Takashi, Goto, Mariko, Fukuta, Hiroshi, Kawashimo, Masumi, Fujimoto, Koichiro, Kusumoto, Yasuhide, Motoyoshi, Hidetaka, Shibata, Norio, Abiru, Hironori, Yamasaki, Katsumi, Eguchi
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Journal Title
American Journal of Gastroenterology 101(12)
Pages: 2752-2759
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Distinct responses of two hepatocellular carcinoma cell lines of a similar origin to immunotherapies targeting regulatory or effector T cells2007
Author(s)
Yasuhide, Motoyoshi, Yuji, Nagayama, Wataru, Hase, Ohki, Saitoh, Rintaroh, Sogawa, Kazuhiko, Nakao
Organizer
14th Japan-Korea Hepatitis Meetin
Place of Presentation
Fukuoka, Japan
Year and Date
20070616-17
Description
「研究成果報告書概要(欧文)」より
