Developmental research on dendritic cell-based immunotherapy against chronic hepatitis C and hepatocellular carcinoma

基于树突状细胞的慢性丙型肝炎和肝细胞癌免疫治疗的进展研究

• 批准号: 19590765
• 负责人: KANTO Tatsuya
• 金额: $ 3万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19590765/
• 关键词: 樹状細胞; C型肝炎; Toll様受容体; インターフェロンα; リバビリン; HCVプロテアーゼ阻害剤; Type III IFN; RIG-I

In hepatitis C virus (HCV) infection, it is well known that the impaired function of dendritic cells (DC) is critically involved in the development of liver disease as well as resistance to anti-viral therapy, such as a combination of peg-interferon-a and ribavirin. We demonstrated in this research project that myeloid DC (MDC) are functionally impaired in the production of type-I IFN and IL-12 in response to Toll-like receptor (TLR) signaling, of which is partly due to reduced expression of TRIF and TRAF6 adaptor molecules. In addition, the treatment of MDC with HCV NS3/4A protease inhibitor restored MDC of stimulatory capacity for CD4+ T cells. Therefore, we demonstrate that MDC could be served as a therapeutic target in order to enhance anti-HCV immune reactions.

众所周知，在丙型肝炎病毒(HCV)感染中，树突状细胞(DC)的功能受损与肝病的发生以及抗病毒治疗(如联合使用干扰素和利巴韦林)的耐药密切相关。我们在本研究项目中证实，髓样DC(MDC)在Toll样受体(TLR)信号作用下产生I型干扰素和IL-12的功能受损，部分原因是TRIF和TRAF6接头分子表达减少。此外，用丙型肝炎病毒NS3/4A蛋白水解酶抑制剂处理MDC后，MDC对CD4+T细胞的刺激能力有所恢复。因此，我们证明MDC可以作为一个治疗靶点，以增强抗丙型肝炎病毒的免疫反应。

项目成果

IL-7 as a booster of Th2-differentiation by modulating myeloid dendritic cells in chronic hepatitis C virus infection

IL-7 通过调节慢性丙型肝炎病毒感染中的骨髓树突状细胞来促进 Th2 分化

• 发表时间: 2008
• 作者: Takebe S.;Kanto T.;et al
• 通讯作者: et al

Feasibility of IL-10-producing regulatory Type 1 cells for the monitoring of viable hepatocellular carcinoma through local ablation therapy.

产生 IL-10 的调节性 1 型细胞通过局部消融治疗监测活肝细胞癌的可行性。

• 发表时间: 2009
• 作者: Kakita N;Kanto T;et. al.
• 通讯作者: et. al.

Involvement of dendritic cell frequency and function in virological relapse in pegylated interferon-α2b and ribavirin therapy for chronic hepatitis C patients.

慢性丙型肝炎患者聚乙二醇干扰素-α2b 和利巴韦林治疗中树突状细胞频率和功能与病毒学复发的关系。

• 发表时间: 2007
• 期刊: Journal of Medical Virology 79
• 作者: Itose I.;Kanto T.;Inoue;M.;Miyazaki;M.;Miyatake;H.;Sakakibara;M.;Yakushijin;T.;Oze;T.;Hiramatsu;N.;Takehara;T.;Kasahara;A.;Hayashi;N.
• 通讯作者: N.

Replication-competent recombinant vesicular stomatitis virus encoding hepatitis C virus envelope proteins

• DOI: 10.1128/jvi.00608-07
• 发表时间: 2007-08-01
• 期刊: JOURNAL OF VIROLOGY
• 影响因子: 5.4
• 作者: Tani, Hideki;Komoda, Yasumasa;Matsuura, Yoshiharu
• 通讯作者: Matsuura, Yoshiharu

Mcl-1 and Bcl-xL cooperatively maintain integrity of hepatocytes in developing and adult murine liver.

• DOI: 10.1002/hep.23126
• 发表时间: 2009-10
• 期刊: HEPATOLOGY
• 影响因子: 13.5
• 作者: Hikita, Hayato;Takehara, Tetsuo;Shimizu, Satoshi;Kodama, Takahiro;Li, Wei;Miyagi, Takuya;Hosui, Atsushi;Ishida, Hisashi;Ohkawa, Kazuyoshi;Kanto, Tatsuya;Hiramatsu, Naoki;Yin, Xiao-Ming;Hennighausen, Lothar;Tatsumi, Tomohide;Hayashi, Norio
• 通讯作者: Hayashi, Norio