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Identification of the sub-population in human malignant melanoma showing strong resistance to tumor specific cytotoxic T cells

Research Project

Project/Area Number 15K09783
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Dermatology
Research InstitutionKeio University

Principal Investigator

Yaguchi Tomonori  慶應義塾大学, 医学部(信濃町), 講師 (40424163)

Co-Investigator(Kenkyū-buntansha) 河上 裕  慶應義塾大学, 医学部(信濃町), 教授 (50161287)
Co-Investigator(Renkei-kenkyūsha) INOZUME Takashi  山梨大学, 医学部, 専任講師 (80334853)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords悪性黒色腫 / 免疫療法 / がん免疫療法
Outline of Final Research Achievements

Although cancer immunotherapies have become one of the major treatment for malignant melanoma (MM), only 20-30% of patients can show objective clinical responses. Unresponsiveness to immunotherapies may be mediated by numerous immunosuppressive mechanisms that inhibit anti-tumor T-cell responses. Thus, combined therapies that can reverse immunosuppression in non-responders and identification of biomarkers for responders are urgently needed. In this study, we have identified three cell surface markers which could define particular subpopulation showing resistance to tumor antigen specific cytotoxic T cells. Moreover, by cDNA microarray analysis, we also identified the one responsible gene that directly caused this resistance. These results indicate that these cell surface markers and the gene may be potential biomarkers for the prediction of responders for immunotherapies and could be used as attractive therapeutic targets in MM.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (32 results)

All 2017 2016 2015

All Journal Article (10 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Open Access: 3 results,  Acknowledgement Compliant: 2 results) Presentation (22 results) (of which Int'l Joint Research: 2 results,  Invited: 9 results)

  • [Journal Article] Human PBMC-transferred murine MHC class I/II-deficient NOG mice enable long-term evaluation of human immune responses2017

    • Author(s)
      Yaguchi Tomonori、Kobayashi Asuka、Inozume Takashi、Morii Kenji、Nagumo Haruna、Nishio Hiroshi、Iwata Takashi、Ka Yuyo、Katano Ikumi、Ito Ryoji、Ito Mamoru、Kawakami Yutaka
    • Journal Title

      Cell Mol Immunol.

      Volume: 印刷中 Issue: 11 Pages: 1-10

    • DOI

      10.1038/cmi.2017.106

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 癌免疫応答の制御方法/ 免疫制御剤②化学療法剤以外の薬剤2017

    • Author(s)
      谷口智憲、河上裕
    • Journal Title

      実験医学

      Volume: 34 Pages: 1967-1975

    • Related Report
      2017 Annual Research Report
  • [Journal Article] 免疫チェックポイント阻害を中心とした複合がん免疫療法2017

    • Author(s)
      谷口智憲、河上裕
    • Journal Title

      Current Therapy

      Volume: 35 Pages: 68-73

    • Related Report
      2017 Annual Research Report
  • [Journal Article] がん免疫治療をベースとした併用治療2017

    • Author(s)
      谷口智憲、河上裕
    • Journal Title

      Vita

      Volume: 35 Pages: 71-77

    • Related Report
      2017 Annual Research Report
  • [Journal Article] 免疫チェックポイント阻害を中心とした複合がん免疫療法2017

    • Author(s)
      谷口智憲、河上裕
    • Journal Title

      Current therapy

      Volume: 35 Pages: 166-171

    • Related Report
      2016 Research-status Report
  • [Journal Article] Prognostic value of tumor-infiltrating lymphocytes differs depending on histological type and smoking habit in completely resected non-small-cell lung cancer.2016

    • Author(s)
      Kinoshita T, Muramatsu R, Fujita T, Nagumo H, Sakurai T, Noji S, Takahata E, Yaguchi T, Tsukamoto N, Kudo-Saito C, Hayashi Y, Kamiyama I, Ohtsuka T, Asamura H, Kawakami Y.
    • Journal Title

      Ann Oncol.

      Volume: 27 Issue: 11 Pages: 2117-2123

    • DOI

      10.1093/annonc/mdw319

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Cancer-induced heterogeneous immunosuppressive tumor microenvironments and their personalized modulation.2016

    • Author(s)
      Yaguchi T, Kawakami Y.
    • Journal Title

      Int. Immunol.

      Volume: 28 Issue: 8 Pages: 393-399

    • DOI

      10.1093/intimm/dxw030

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 複合がん免疫療法2016

    • Author(s)
      谷口智憲、河上裕
    • Journal Title

      Pharma Medica

      Volume: 34 Pages: 59-63

    • Related Report
      2016 Research-status Report
  • [Journal Article] 免疫制御剤② シグナル阻害剤、IDO阻害剤、COX2阻害剤、CSF-1受容体阻害剤など2016

    • Author(s)
      谷口智憲、河上裕
    • Journal Title

      実験医学

      Volume: 34 Pages: 1967-1975

    • Related Report
      2016 Research-status Report
  • [Journal Article] Melanoma cells control anti-melanoma CTL responses via interaction between TIGIT and CD155 in the effector phase.2016

    • Author(s)
      Inozume T, Yaguchi T, Furuta F, Harada K, Kawakami Y, Shimada S.
    • Journal Title

      J Invest Dermatol.

      Volume: 136 Issue: 1 Pages: 255-263

    • DOI

      10.1038/jid.2015.404

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] Immunobiology and immunotherapy for gynecological cancers2017

    • Author(s)
      Yutaka Kawakami, Tomonori Yaguchi, Taeko Hayakwa, Kinya Tsubota, Juri Sugiyama, Takashi Nishio, Taku Iwata, Tomonobu Fujita, Daisuke Aoki.
    • Organizer
      The 5thBiennial Meeting of Asian Society of Gynecologic Oncology
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] スタチン系製剤は制御性T細胞を抑制し抗腫瘍免疫応答を増強する2017

    • Author(s)
      坪田欣也、谷口智憲、後藤浩、河上裕
    • Organizer
      第45回日本臨床免疫学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] CSF-1受容体阻害による腫瘍関連マクロファージ制御を介したPD-1阻害療法の抵抗性改善と治療効果増強2017

    • Author(s)
      田宮将樹、守井賢二、谷口智憲、河上裕
    • Organizer
      第45回日本臨床免疫学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 癌微小環境における免疫回避抑制機構とその克服法2017

    • Author(s)
      谷口智憲、藤田知信、河上裕
    • Organizer
      第26回日本がん転移学会学術集会・総会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] スタチン系製剤はmTORC1を介して制御性T細胞を制御し抗腫瘍免疫応答を増強する2017

    • Author(s)
      坪田欣也、谷口智憲、守井賢二、河上裕
    • Organizer
      第21回日本がん免疫学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 新規腫瘍抗原グリピカン-1を標的としたキメラ抗原受容体遺伝子導入T細胞は正常組織への副作用なく強い抗腫瘍活性を示す2017

    • Author(s)
      加藤大貴、谷口智憲、守井賢二、世良田聡、仲哲治、中川貴之、西村亮平、河上裕
    • Organizer
      第21回日本がん免疫学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 4-1BB刺激は免疫チェックポイント阻害と相乗的にメラノーマ特異的CTLの活性を増強する2017

    • Author(s)
      猪爪隆史、谷口智憲、河上裕
    • Organizer
      第21回日本がん免疫学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] A BRAF inhibitor and a Toll-like receptor 7 agonist synergistically enhanced anti-tumor immune resonses depending on CD8+ T cell2017

    • Author(s)
      Nakamura Kenta, Yaguchi Tomonori, Murata Masashi, Ota Yosuke, Kiniwa Yukiko, Okuyama Ryuhei, Kawakami Yutaka.
    • Organizer
      The 42thAnnual Meeting of the Japanese Society for Investigative Dermatology
    • Related Report
      2017 Annual Research Report
  • [Presentation] Immunomodulation of ovarian clear cell carcinoma by targeting HNF-1β-NH-kB-IL6 pathway enhances anti-tumor immunity.2017

    • Author(s)
      Kagawa Masaki, Yaguchi Tomonori, Morii Kenji, Takise Yoshiaki, Nishio Hiroshi, Sugiyama Juri, Iwata Takashi, Fujita Tomonobu, Kawakami Yutaka
    • Organizer
      第46回日本免疫学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Reversal of anti-PD-1/PD-L1 therapy resistance by modulation of tumor-associated macrophages using CSF-1 receptor blockade.2017

    • Author(s)
      Tamiya Masaki, Yaguchi Tomonori, Morii Kenji, Kawakami Yutaka
    • Organizer
      第46回日本免疫学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] IL-8 has a negative role on tumor infiltrating CD8+T cells in various cancers.2017

    • Author(s)
      Sayem Mohammad A, Yaguchi Tomonori, Noji Shinobu, Iwata Takashi, Fujita Tomonobu, Kawakami Yutaka.
    • Organizer
      第46回日本免疫学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 症例ごとの免疫状態評価に基づいた個別化がん免疫療法2016

    • Author(s)
      河上裕、藤田知信、谷口智憲
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-10-07
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] がんシグナル伝達分子阻害薬を用いた、がん微小環境の免疫抑制解除による、がん免疫療法の増強2016

    • Author(s)
      谷口智憲、里見良輔、西尾浩、早川妙香、坪田欣也、河上裕
    • Organizer
      第44回日本臨床免疫学会総会
    • Place of Presentation
      京王プラザホテル(東京都新宿区)
    • Year and Date
      2016-09-08
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] がんシグナル伝達分子阻害薬による免疫抑制の解除2016

    • Author(s)
      谷口智憲、岩田 卓、里見 良輔、守井 賢二、西尾 浩、杉山 重里、中村 謙太、香川 昌樹、藤田 知信、河上 裕
    • Organizer
      第20回日本がん免疫学会
    • Place of Presentation
      大阪国際交流センター(大阪府大阪市)
    • Year and Date
      2016-07-29
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 既存薬を用いた、がん微小環境の免疫抑制解除による、免疫チェックポイント阻害薬の抗腫瘍効果の増強2016

    • Author(s)
      谷口 智憲、中村 謙太、早川 妙香、坪田 欣也、河上 裕
    • Organizer
      第20回日本がん免疫学会
    • Place of Presentation
      大阪国際交流センター(大阪府大阪市)
    • Year and Date
      2016-07-28
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] ヒト腫瘍免疫学の最近の進歩とがん免疫療法の展望2016

    • Author(s)
      谷口智憲、河上裕
    • Organizer
      第79回日本皮膚科学会東京・東部支部合同学術集会
    • Place of Presentation
      京王プラザホテル(東京都新宿区)
    • Year and Date
      2016-02-20
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Co-blockade of TIGIT and PD-1 signals in tumor-infiltrating cytotoxic T lymphocytes is an effective antimelanoma therapy2015

    • Author(s)
      Takashi Inozume, Tomonori Yaguchi, Junpei Furuta, Kazutoshi Harada, Yutaka Kawakami, Shinji Shimada
    • Organizer
      第40回日本研究皮膚科学会
    • Place of Presentation
      岡山コンベンションセンター(岡山県岡山市)
    • Year and Date
      2015-12-11
    • Related Report
      2015 Research-status Report
  • [Presentation] ヒトがん微小環境の免疫学的評価 =T細胞の腫瘍浸潤を規定する因子の解析=2015

    • Author(s)
      谷口智憲
    • Organizer
      Human immunology forum
    • Place of Presentation
      京王プラザホテル札幌(北海道札幌市)
    • Year and Date
      2015-11-21
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] The screening for drugs which augment anti-tumor activity of tumor specific effector T cells2015

    • Author(s)
      Takise Yoshiaki, Yaguchi Tomonori, Sunthamala Nuchsupha, Kawakami Yutaka
    • Organizer
      第44回日本免疫学会
    • Place of Presentation
      札幌コンベンションセンター(北海道札幌市)
    • Year and Date
      2015-11-18
    • Related Report
      2015 Research-status Report
  • [Presentation] CD155/TIGITシグナルは悪性黒色腫において腫瘍抗原特異的T細胞応答をエフェクターフェーズで制御する2015

    • Author(s)
      谷口智憲、猪爪隆史、古田潤平、原田和俊、島田眞路、河上裕
    • Organizer
      第43回日本臨床免疫学会総会,
    • Place of Presentation
      神戸国際会議場(兵庫県神戸市)
    • Year and Date
      2015-10-22
    • Related Report
      2015 Research-status Report
  • [Presentation] Combined cancer immunotherapies using molecular-targeting drugs.2015

    • Author(s)
      Yaguchi T.
    • Organizer
      The 4th CSI/JSI/KAI Joint Symposium on Immunology(日本・中国・韓国合同シンポジウム)
    • Place of Presentation
      蘇州(中国)
    • Year and Date
      2015-09-19
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] CD155-TIGIT interaction is an immune checkpoint regulating antimelanoma TIL responses2015

    • Author(s)
      Inozume Takashi, Yaguchi Tomonori, Kawakami Yutaka, Shimada Shinji
    • Organizer
      がん免疫療法・マクロファージ国際会議2015
    • Place of Presentation
      東京大学伊藤国際学術センター内伊藤謝恩ホール(東京都文京区)
    • Year and Date
      2015-07-09
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2019-03-29  

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