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Elucidation of the resistance mechanisms of immunotherapy by the abnormal signal transduction in melanoma and development of methods to overcome it

Research Project

Project/Area Number 21591445
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Dermatology
Research InstitutionKeio University

Principal Investigator

SAKURAI Toshiharu  慶應義塾大学, 医学部, 助教 (20101933)

Co-Investigator(Kenkyū-buntansha) FUJITA Tomonobu  慶應義塾大学, 医学部, 助教 (20199334)
TSUKAMOTO Nobuo  慶應義塾大学, 医学部, 助教 (20407117)
KAWAKAMI Yutaka  慶應義塾大学, 医学部, 教授 (50161287)
Research Collaborator KAWAMURA Naoshi  慶應義塾大学, 医学部, 博士 (30570246)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords皮膚腫瘍学 / 悪性黒色腫 / 免疫抑制 / 免疫療法 / シグナル伝達異常 / 樹状細胞 / シグナル伝達
Research Abstract

In this study, we have attempted to identify new signaling molecules which trigger multiple immunosuppressive and tumor promoting cytokines and chemokines. By screening dendritic cell(DC) suppressing activity of culture supernatants from the human melanoma cell line treated with human kinase siRNA library, we found 7 kinases. One of them, Serine/Threonine kinase 24(STK24), was found to induce production of IL10, TGF-β, and CCL2 by human melanoma cells. Phosphorylated STK24 was increased in various human melanoma cell lines and melanoma tissue. These results indicate that activated STK24 in cancer cells is involved in the generation of tumor promoting and immunosuppressive tumor microenvironment.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (29 results)

All 2011 2010 2009

All Journal Article (8 results) (of which Peer Reviewed: 7 results) Presentation (20 results) Book (1 results)

  • [Journal Article] Enhanced Cancer Immunotherapy Using STAT3-Depleted Dendritic cells with High Th1-Inducing Ability and Resistance to Cancer Cell-Derived Inhibitory Factors2011

    • Author(s)
      Iwata-Kajihara T, Sumimoto H, Kawamura N, Ueda R, Takahashi T, Mizuguchi H, Miyagishi M, Takeda K, Kawakami Y
    • Journal Title

      The Journal of Immunology

      Volume: Vol.187, No.1 Pages: 27-36

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article]2011

    • Author(s)
      Yaguchi T, Sumimoto H, Kudo-Saito C, Tsukamoto N, Ueda R, Iwata-Kajihara T, Nishio H, Kawamura N, Kawakami Y
    • Journal Title

      Int J Hematol

      Volume: Vol.93, No.3 Pages: 294-300

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] 癌微小環境におけるPD-L1/PD-1による免疫抑制病態とその是正2011

    • Author(s)
      川村直、谷口智憲、桜井敏晴、河上裕
    • Journal Title

      臨床免疫・アレルギー科

      Volume: Vol.56, No.1 Pages: 1-6

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] The mechanisms of cancer immunoescape and development of overcoming strategies2011

    • Author(s)
      Yaguchi T, et al
    • Journal Title

      Int J Hematol

      Volume: 93(3) Issue: 3 Pages: 294-300

    • DOI

      10.1007/s12185-011-0799-6

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Aberrant Fatty Acid-Binding Protein 7 Gene Expression In Cutaneous Malignant Melanoma2010

    • Author(s)
      Goto Y, Koyanagi K, Narita N, Kawakami Y, Takata M, Uchiyama A, Nguyen L, Nguyen T, Morton DL, Hoon D
    • Volume
      Vol.130, No.1
    • Pages
      221-229
    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Impairment of pDC for IFN production by the ligand for immunoglobulin-like transcript 7(ILT7) expressed on human cancer cells2009

    • Author(s)
      Tsukamoto N, Okada S, Onami Y, Sasaki Y, Umezawa K, Kawakami Y
    • Journal Title

      Clin Cancer Res

      Volume: Vol.15, No.18 Pages: 5733-43

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cancer metastasisi is accelerated through immunosuppression during EMT of cancer cell2009

    • Author(s)
      Kudo-Saito C, Shirako H, Takeuchi T, Kawakami Y
    • Journal Title

      Cancer Cell

      Volume: Vol.16, No.3 Pages: 195-206

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] 腫瘍免疫制御機構とその克服2009

    • Author(s)
      河上裕、住本秀敏、工藤千恵、塚本信夫、桜井敏晴、植田良、谷口智憲、川村直、梶原知子
    • Journal Title

      最新医学

      Volume: Vol.64、No.11

    • Related Report
      2011 Final Research Report
  • [Presentation] Poor responses to dendritic cell immunotherapy in patients with high serum cytokines related to chronic inflammation2011

    • Author(s)
      Kawase Y、Sakurai T、Kawakami Y, その他
    • Organizer
      第70回日本癌学会
    • Place of Presentation
      愛知県・名古屋国際会議場
    • Year and Date
      2011-10-05
    • Related Report
      2011 Annual Research Report
  • [Presentation] Enhanced metastasis through immunosuppressive cancer microenvironment and its control by targeting signaling molecules2011

    • Author(s)
      Kawakami Y, Tsukamoto N, その他
    • Organizer
      第70回日本癌学会総会
    • Place of Presentation
      名古屋国際会議場、名古屋
    • Year and Date
      2011-10-04
    • Related Report
      2011 Final Research Report
  • [Presentation] Roles of STAT3 in dendritic cells in cancer induced immunosuppression and its control for effective immunotherapy2011

    • Author(s)
      Kawamura N, Kawakami Y, その他
    • Organizer
      第70回日本癌学会総会
    • Place of Presentation
      名古屋国際会議場、名古屋
    • Year and Date
      2011-10-04
    • Related Report
      2011 Final Research Report
  • [Presentation] Poor responses to dendritic cell immunotherapy in patients with high serum cytokines related to chronic inflammation2011

    • Author(s)
      Kawase Y, Sakurai T, Fujita T, Kawakami Y, その他
    • Organizer
      第70回日本癌学会総会
    • Place of Presentation
      名古屋国際会議場、名古屋
    • Year and Date
      2011-10-04
    • Related Report
      2011 Final Research Report
  • [Presentation] Enhanced metastasis through immunosuppressive cancer microenvironment and its control by targeting signaling molecules2011

    • Author(s)
      Kawakami Y、Tsukamoto N, その他
    • Organizer
      第70回日本癌学会
    • Place of Presentation
      愛知県・名古屋国際会議場
    • Year and Date
      2011-10-04
    • Related Report
      2011 Annual Research Report
  • [Presentation] Roles of STAT3 in dendritic cells in cancer induced immunosuppression and its control for effective immunotherapy2011

    • Author(s)
      Kawamura N、Kawakami Y, その他
    • Organizer
      第70回日本癌学会
    • Place of Presentation
      愛知県・名古屋国際会議場
    • Year and Date
      2011-10-04
    • Related Report
      2011 Annual Research Report
  • [Presentation] Histatin-1 enhances metastatic and immunosuppressive activity of human malignant melanoma2011

    • Author(s)
      Yaguchi T, Kawakami Y, その他
    • Organizer
      第70回日本癌学会総会
    • Place of Presentation
      名古屋国際会議場、名古屋
    • Year and Date
      2011-10-03
    • Related Report
      2011 Final Research Report
  • [Presentation] Histatin-1 enhances metastatic and immunosuppressive activity of human malignant melanoma2011

    • Author(s)
      Yaguchi T、Kawakami Y, その他
    • Organizer
      第70回日本癌学会
    • Place of Presentation
      愛知県・名古屋国際会議場
    • Year and Date
      2011-10-03
    • Related Report
      2011 Annual Research Report
  • [Presentation] がん免疫逃避機構とその制御2011

    • Author(s)
      河上裕、塚本信夫, その他
    • Organizer
      第15回日本がん免疫学会総会
    • Place of Presentation
      大阪府・千里ライフサイエンスセンター、大阪
    • Year and Date
      2011-07-01
    • Related Report
      2011 Final Research Report
  • [Presentation] がん免疫逃避機構とその制御2011

    • Author(s)
      河上裕、塚本信夫, その他
    • Organizer
      第15回日本がん免疫学会
    • Place of Presentation
      大阪府・千里ライフサイエンスセンター
    • Year and Date
      2011-07-01
    • Related Report
      2011 Annual Research Report
  • [Presentation] 悪性黒色腫に異所性に発現するHistatin-1は細胞運動能と免疫抑制能を亢進させる2011

    • Author(s)
      谷口智憲、河上裕, その他
    • Organizer
      第15回日本がん免疫学会総会
    • Place of Presentation
      大阪府・千里ライフサイエンスセンター、大阪
    • Year and Date
      2011-06-30
    • Related Report
      2011 Final Research Report
  • [Presentation] がん微小環境免疫抑制病態における樹状細胞STAT3の意義とその制御2011

    • Author(s)
      川村直、河上裕, その他
    • Organizer
      第15回日本がん免疫学会総会
    • Place of Presentation
      大阪府・千里ライフサイエンスセンター、大阪
    • Year and Date
      2011-06-30
    • Related Report
      2011 Final Research Report
  • [Presentation] 悪性黒色腫に異所性に発現するHistatin-1は細胞運動能と免疫抑制能を亢進させる2011

    • Author(s)
      谷口智憲、河上裕, その他
    • Organizer
      第15回日本がん免疫学会
    • Place of Presentation
      大阪府・千里ライフサイエンスセンター
    • Year and Date
      2011-06-30
    • Related Report
      2011 Annual Research Report
  • [Presentation] がん微小環境免疫抑制病態における樹状細胞STAT3の意義とその制御2011

    • Author(s)
      川村直、河上裕, その他
    • Organizer
      第15回日本がん免疫学会
    • Place of Presentation
      大阪府・千里ライフサイエンスセンター
    • Year and Date
      2011-06-30
    • Related Report
      2011 Annual Research Report
  • [Presentation] Possible improvement of cancer immunotherapy based on the analyses of anti-tumor immune responses in human2010

    • Author(s)
      Yutaka Kawakami, Nobuo Tsukamoto, Tomonobu Fujita, Toshiharu Sakurai, Tomonori Yaguchi
    • Organizer
      金沢国際がん生物学シンポジュウム
    • Place of Presentation
      KKRホテル金沢、金沢
    • Year and Date
      2010-08-29
    • Related Report
      2011 Final Research Report
  • [Presentation] Possible improvement of cancer immunotherapy based on the analyses of anti-tumor immune responses in human2010

    • Author(s)
      Yutaka Kawakami
    • Organizer
      金沢国際がん生物学シンポジュウム
    • Place of Presentation
      KKRホテル金沢
    • Year and Date
      2010-08-29
    • Related Report
      2010 Annual Research Report
  • [Presentation] Immune escape of human melanoma via activated Wnt/β-catenin signaling2010

    • Author(s)
      Tomonori Yaguchi
    • Organizer
      14^<th> International Congress of Immunology
    • Place of Presentation
      Kobe International Convention Center
    • Year and Date
      2010-08-25
    • Related Report
      2010 Annual Research Report
  • [Presentation] 悪性黒色腫および樹状細胞でのWnt/β-cateninシグナル亢進はがん微小環境での免疫抑制に関与する2010

    • Author(s)
      谷口智憲、桜井敏晴、塚本信夫、藤田知信、河上裕
    • Organizer
      第14回日本がん免疫学会総会
    • Place of Presentation
      KKRホテル熊本、熊本
    • Year and Date
      2010-07-23
    • Related Report
      2011 Final Research Report
  • [Presentation] 悪性黒色腫および樹状細胞でのWnt/β-cateninシグナル亢進はがん微小環境での免疫抑制に関与する2010

    • Author(s)
      谷口智憲
    • Organizer
      第14回日本がん免疫学会
    • Place of Presentation
      KKRホテル熊本
    • Year and Date
      2010-07-23
    • Related Report
      2010 Annual Research Report
  • [Presentation] 悪性黒色腫に対する免疫応答と免疫療法-最近の進歩-2009

    • Author(s)
      河上裕
    • Organizer
      第22回日本色素細胞学会総会
    • Place of Presentation
      電気ビル、福岡
    • Year and Date
      2009-12-05
    • Related Report
      2011 Final Research Report
  • [Book] がん関連微小環境における免疫抑制とその制御、バイオテクノロジーシリーズがん免疫療法-実用化へのチャレンジ-2010

    • Author(s)
      河上裕
    • Publisher
      シーエムシー出版
    • Related Report
      2011 Final Research Report

URL: 

Published: 2009-04-01   Modified: 2016-04-21  

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