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Elucidation of Tumor Immune Escape Mechanisms Promoted Lymph Node Metastasis

Research Project

Project/Area Number 25461971
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General surgery
Research InstitutionAkita University

Principal Investigator

Imai Kazuhiro  秋田大学, 医学部, 講師 (70396555)

Co-Investigator(Kenkyū-buntansha) MINAMIYA Yoshihiro  秋田大学, 大学院医学系研究科, 教授 (30239321)
工藤 智司  秋田大学, 医学部, その他 (80638271)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsTGF-β1 / 樹状細胞 / センチネルリンパ節 / リンパ節転移 / がん免疫逃避機構 / 腫瘍免疫逃避機構 / 転移
Outline of Final Research Achievements

Transforming growth factor (TGF)-βis known to be produced by progressor tumors and to immobilize dendritic cells (DCs) within those tumors. Moreover, although TGF-β1 has been shown to promote tumor progression, there is still no direct evidence as to whether TGF-β1 is able to directly induce distant metastasis. To address that issue and investigate the mechanism by which TGF-β1 suppresses DC, B cell, and T cell activity in tumor draining lymph node (TDLN), we subdermally inoculated mouse ears with squamous cell carcinoma cells stably expressing TGF-β1 or empty vector (mock). Two weeks after inoculation, the mice were sacrificed, and the neck TDLN was excised. TDLN from mice inoculated with TGF-β1 clone showed significantly lower levels of CCL19, CCL21, and IL-4 mRNA than mock. In addition, we found that DCs, B cells, CD40L+ Tfh cells, and CD4+CXCR5+CCR7- subset were reduced in mice inoculated with TGF-β1 clone. These findings suggest TGF-β1 inhibits early immunological memory.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (1 results)

All 2013

All Presentation (1 results)

  • [Presentation] Transforming growth factor-beta 1 enables tumors to escape the dendritic cell-mediated immune response, and increases tumor-draining lymph node metastasis.2013

    • Author(s)
      今井一博
    • Organizer
      the 8th International Sentinel Node Society (ISNS) Meeting
    • Place of Presentation
      San Francisco, California
    • Related Report
      2013 Research-status Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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