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Microenvironment in hepatocellular carcinoma

Research Project

Project/Area Number 24390320
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Digestive surgery
Research InstitutionKyushu University

Principal Investigator

SHIRABE Ken  九州大学, 医学(系)研究科(研究院), 准教授 (70264025)

Co-Investigator(Kenkyū-buntansha) TAKENOYAMA Mitsuhiro  九州がんセンター臨床研究センター, その他部局等, 呼吸器腫瘍科科長 (10309966)
SOEJIMA Yuji  九州大学, 医学研究院, 共同研究員 (30325526)
YONEMITSU Yoshikazu  九州大学, 薬学研究院, 教授 (40315065)
MAEHARA Yoshihiko (AISHIMA Shinichi)  九州大学, 医学研究院, 教授 (80165662)
YOSHIZUMI Tomoharu  九州大学, 大学病院, 講師 (80363373)
IKEGAMI Toru  九州大学, 大学病院, 助教 (80432938)
OKANO Shinji  九州大学, 医学研究院, 准教授 (10380429)
相島 慎一  佐賀大学, 医学部, 教授 (70346774)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
Fiscal Year 2014: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2012: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
Keywords肝臓外科学 / PD-L1 / HLA I / 肝細胞癌 / HLA I / 腫瘍関連マクロファージ / STAT3 / Il-17
Outline of Final Research Achievements

We have shown tumor associated macrophage (TAM) accelerates malignant potential in hepatocellular carcinoma (HCC). Expression of programmed cell death 1 (PD L1) and human leukocyte antigen class I (HLA I) were examined in HCC in the resected specimens. PD-L1 expression was significantly correlated with TAM accumulation and the patients with PD-L1 negative and HLA I positive HCC had favorable prognosis. This suggests that blockade of PD-L1 and PD-1 pathway might be effective therapeutic strategy. In our recent study, PD-L1 expression was significantly correlated with immune suppression and epithelial mesenchymal transition of cancer cells in pancreatic cancer.
To clarify the relationship among IL-17, TAM, PD-1, and PD-L1, subcutaneous tumor model, using IFN sensitive mouse HCC cell line, was established. This model was planned to be applied to IL17KO、and IFN-γKO mouse. Nevertheless, IL17 expression was unstable and we have gotten new KO mouse and we have continued this experiment.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (8 results)

All 2015 2014 2013

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 1 results) Presentation (3 results) (of which Invited: 1 results)

  • [Journal Article] Prognostic impact of programmed cell death 1 ligand 1 expression in human leukocyte antigen class I-positive hepatocellular carcinoma after curative hepatectomy.2014

    • Author(s)
      Umemoto Y, Okano S, Matsumoto Y, Nakagawara H, Matono R, Yoshiya S, Yamashita YI, Yoshizumi T, Ikegami T, Soejima Y, Harada M, Aishima S, Oda Y, Shirabe K, Maehara Y.
    • Journal Title

      J Gastroenterol.

      Volume: not determined Issue: 1 Pages: 65-75

    • DOI

      10.1007/s00535-014-0933-3

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prognostic factors affecting survival at recurrence of hepatocellular carcinoma after living-donor liver transplantation: with special reference to neutrophil/lymphocyte ratio.2013

    • Author(s)
      Harimoto N, Shirabe K, Nakagawara H, Toshima T, Yamashita Y, Ikegami T, Yoshizumi T, Soejima Y, Ikeda T, Maehara Y.
    • Journal Title

      Transplantation

      Volume: 96(11) Issue: 11 Pages: 1008-12

    • DOI

      10.1097/tp.0b013e3182a53f2b

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tumor-Associated Macrophage Promotes Tumor Progression via STAT3 Signaling in Hepatocellular Carcinoma.2013

    • Author(s)
      119. Mano Y, Aishima S, Fujita N, Tanaka Y, Kubo Y, Motomura T, Taketomi A, Shirabe K, Maehara Y, Oda Y.
    • Journal Title

      Pathobiology.

      Volume: 80 Issue: 3 Pages: 146-154

    • DOI

      10.1159/000346196

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impact of tumor size, number of tumors and neutrophil-to-lymphocyte ratio in liver transplantation for recurrent hepatocellular carcinoma.2013

    • Author(s)
      Yoshizumi T, Ikegami T, Yoshiya S, Motomura T, Mano Y, Muto J, Ikeda T, Soejima Y, Shirabe K, Maehara Y.
    • Journal Title

      Hepatol Res.

      Volume: 43 Issue: 7 Pages: 709-16

    • DOI

      10.1111/hepr.12016

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neutrophil-lymphocyte ratio reflects hepatocellular carcinoma recurrence after liver transplantation via inflammatory microenvironment.2013

    • Author(s)
      Motomura T, Yoshizumi T, et al
    • Journal Title

      Journal of Hepatology

      Volume: 58 Issue: 1 Pages: 58-64

    • DOI

      10.1016/j.jhep.2012.08.017

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] 膵癌における間葉系形質の獲得とPD-L1の発現に関する臨床病理学的検討2015

    • Author(s)
      今井大祐、調  憲ほか
    • Organizer
      第36回癌免疫外科研究会
    • Place of Presentation
      奄美観光ホテル
    • Year and Date
      2015-05-14 – 2015-05-15
    • Related Report
      2014 Annual Research Report
  • [Presentation] 進行肝癌における炎症マーカーの意義2014

    • Author(s)
      調  憲
    • Organizer
      第50回日本肝癌研究会
    • Place of Presentation
      京都国際会議場
    • Year and Date
      2014-06-05 – 2014-06-06
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 肝細胞癌外科的治療における術前末梢血好中球リンパ球比(Neutrophil/lymphocyte ratio : NLR)の意義2013

    • Author(s)
      間野洋平
    • Organizer
      第113回日本外科学会定期学術集会
    • Place of Presentation
      福岡マリンメッセ
    • Year and Date
      2013-04-11
    • Related Report
      2012 Annual Research Report

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Published: 2012-04-24   Modified: 2019-07-29  

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