• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Enhancement of anti-tumor immune responses by EGFR-TKIs (EGFR- tyrosin kinase inhibitors)

Research Project

Project/Area Number 25830122
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Tumor therapeutics
Research InstitutionKeio University

Principal Investigator

YAGUCHI Tomonori  慶應義塾大学, 医学部, 助教 (40424163)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsがん免疫療法 / 肺癌 / EGFR-TKI / 免疫抑制
Outline of Final Research Achievements

In this study, we evaluated the enhancement of anti-tumor immune responses by EGFR-tyrosine kinase inhibitor (TKI) in non-small cell lung carcinoma cell (NSCLC). Human NSCLC with mutated EGFR produced immunosuppressive cytokines and suppressed human DC function, which were restored by EGFR-TKI pretreatment of NSCLC. EGFR-TKI directly enhanced human DC function in an EGFR-independent manner. Moreover, in vivo administration of EGFR-TKI augmented tumor antigen-specific T cell induction and enhanced anti-tumor effects of immunotherapies. These results indicate that EGFR-TKIs may have an activity to enhance antitumor immune responses for NSCLC by targeting both cancer cells and DC, and combined use of EGFR-TKIs may augment the therapeutic effects of current immunotherapies.

Report

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

    (36 results)

All 2014 2013

All Journal Article (13 results) (of which Peer Reviewed: 6 results,  Open Access: 2 results) Presentation (23 results) (of which Invited: 2 results)

  • [Journal Article] Immunosuppression through constitutively activated NF-κB signalling in human ovarian cancer and its reversal by an NF-κB inhibitor.2014

    • Author(s)
      Nishio H, Yaguchi T, Sugiyama J, Sumimoto H, Umezawa K, Iwata T, Susumu N,Fujii T, Kawamura N, Kobayashi A, Park J, Aoki D, Kawakami Y.
    • Journal Title

      Br J Cancer.

      Volume: 110 Issue: 12 Pages: 2965-74

    • DOI

      10.1038/bjc.2014.251

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] TGF-β1 in tumor microenvironments induces immunosuppression in the tumors and sentinel lymph nodes and promotes tumor progression2014

    • Author(s)
      Nakamura S, Yaguchi T, Kawamura N, Kobayashi A, Sakurai T, Higuchi H, Takaishi H, Hibi T, Kawakami Y
    • Journal Title

      J Immunother

      Volume: 37(2) Issue: 2 Pages: 63-72

    • DOI

      10.1097/cji.0000000000000011

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 抗腫瘍免疫応答の総合的な制御2014

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

      血液フロンティア

      Volume: 24 Pages: 1579-1605

    • Related Report
      2014 Annual Research Report
  • [Journal Article] がんの免疫逃避機構と分子標的薬を用いた免疫応答の制御2014

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

      産科と婦人科

      Volume: 81 Pages: 157-163

    • Related Report
      2013 Research-status Report
  • [Journal Article] がん免疫における免疫チェックポイント機構の意義とその制御によるがん治療2014

    • Author(s)
      河上裕 川村直 ポピバノバ・ボリヤナ 中村謙太 早川妙香 谷口智憲
    • Journal Title

      がん分子標的治療

      Volume: 12 Pages: 15-22

    • Related Report
      2013 Research-status Report
  • [Journal Article] Intratumoral Injection of BCG-CWS-Pretreated Dendritic Cells Following Tumor Cryoablation2014

    • Author(s)
      Kawamura N, Udagawa M, Fujita T, Sakurai T, Yaguchi T, Kawakami Y.
    • Journal Title

      Methods Mol Biol.

      Volume: 1139 Pages: 145-53

    • DOI

      10.1007/978-1-4939-0345-0_13

    • ISBN
      9781493903443, 9781493903450
    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] 化学療法・分子標的薬による免疫応答増強2013

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

      医学のあゆみ

      Volume: 244 Pages: 817-823

    • Related Report
      2013 Research-status Report
  • [Journal Article] 化学療法・分子標的薬による抗腫瘍免疫応答の制御2013

    • Author(s)
      谷口智憲, 里見良輔、西尾浩、杉山重里、大村学、中村謙太、川村直、小林明日香、河上裕
    • Journal Title

      実験医学

      Volume: 31 Pages: 1938-1944

    • Related Report
      2013 Research-status Report
  • [Journal Article] 悪性黒色腫におけるPI3K/AKT経路の役割2013

    • Author(s)
      谷口智憲, 川村直, 中村謙太, 河上裕
    • Journal Title

      日本臨床

      Volume: 71 suppl 4 Pages: 139-143

    • Related Report
      2013 Research-status Report
  • [Journal Article] 抗PD-1抗体、抗PD-L1抗体による免疫療法2013

    • Author(s)
      谷口智憲, 里見良輔, 川村直, 河上裕
    • Journal Title

      日本臨床

      Volume: 71 suppl 6 Pages: 253-257

    • Related Report
      2013 Research-status Report
  • [Journal Article] Cancer-induced immunosuppressive cascades and their reversal by molecular-targeted therapy.2013

    • Author(s)
      Kawakami Y, Yaguchi T, Sumimoto H, Kudo-Saito C, Tsukamoto N, Iwata-Kajihara T, Nakamura S, Nishio H, Satomi R, Kobayashi A, Tanaka M, Hoon Park J, Kamijuku H, Tsujikawa T, Kawamura N
    • Journal Title

      Ann. N.Y. Acad. Sci.,

      Volume: 1284(1) Issue: 1 Pages: 80-86

    • DOI

      10.1111/nyas.12094

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Improvement of cancer immunotherapy by combining molecular targeted therapy2013

    • Author(s)
      Kawakami Y, Yaguchi T, Sumimoto H, Kudo-Saito C, Iwata-Kajihara T, Nakamura S, Miyzaki J, Kawamura N, Hoon Park J, Popivanova B, Tsujikawa T
    • Journal Title

      Frontiers in Oncology

      Volume: 36 Pages: 1-7

    • DOI

      10.3389/fonc.2013.00136

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Angiotensin II type 1 receptor antagonist attenuates lacrimal gland, lung, and liver fibrosis in a murine model of chronic graft-versus-host disease.2013

    • Author(s)
      Yaguchi S, Ogawa Y, Shimmura S, Kawakita T, Hatou S, Satofuka S, Nakamura S, Imada T, Miyashita H, Yoshida S, Yaguchi T, Ozawa Y, Mori T, Okamoto S, Kawakami Y, Ishida S, Tsubota K.
    • Journal Title

      PLoS ONE

      Volume: 8 Issue: 6 Pages: e64724-e64724

    • DOI

      10.1371/journal.pone.0064724

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Effective cancer immunotherapy for human melanoma by combination of BRAF inhibitor and Toll-like receptor 7 agonist2014

    • Author(s)
      Nakamura K, Yaguchi T, Popivanova B, Murata M, Mikoshiba A, Kiniwa Y, Okuyama R, Kawakami Y
    • Organizer
      第43回日本免疫学会学術集会
    • Place of Presentation
      京都
    • Year and Date
      2014-12-10 – 2014-12-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] EGFR-TKIs (EGFR- tyrosin kinase inhibitors) enhance anti-tumor immune responses by acting on both non-small cell lung carcinoma cells and immune cells2014

    • Author(s)
      Yaguchi T, Satomi R, Kobayashi A, Morii K, Kawakami Y.
    • Organizer
      第43回日本免疫学会学術集会
    • Place of Presentation
      京都
    • Year and Date
      2014-12-10 – 2014-12-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] Enhanced anti-tumor effects of the PD-1/PD-L1 blockade by combining a highly absorptive form of NF-kB/STAT3 inhibitor curcumin2014

    • Author(s)
      Hayakawa T, Sugiyama J, Yaguchi T, Imaizumi A, Kawakami Y.
    • Organizer
      Society for Immunotherapy of Cancer 29th Annual Meeting
    • Place of Presentation
      National Harbor, MD, USA.
    • Year and Date
      2014-11-06 – 2014-11-09
    • Related Report
      2014 Annual Research Report
  • [Presentation] 分子標的薬併用による効果的な個別化がん免疫療法2014

    • Author(s)
      河上 裕、早川 妙香、中村 謙太、ボリヤナ ポピバノバ、杉山 重里、西尾 浩、谷口 智憲
    • Organizer
      第73回日本癌学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] ルクミン併用による免疫抑制改善効果を介した免疫チェックポイント阻害療法の効果増強2014

    • Author(s)
      早川 妙香、杉山 重里、谷口 智憲、今泉 厚、河上 裕
    • Organizer
      第73回日本癌学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] CD155-TIGIT interaction is an immune checkpoint regulating antimelanoma immune responses2014

    • Author(s)
      猪爪隆史、谷口智憲、古田潤平、原田和俊、伊藤守、河上裕、島田眞路
    • Organizer
      第18回日本がん免疫学会総会
    • Place of Presentation
      松山
    • Year and Date
      2014-07-30 – 2014-08-01
    • Related Report
      2014 Annual Research Report
  • [Presentation] ヒト末梢血移入マウスMHC class I/IIノックアウトNOGマウスを用いたヒト腫瘍免疫応答のin vivo解析2014

    • Author(s)
      谷口智憲、小林明日香、片野いくみ、何裕遥、猪爪隆史、伊藤守、河上裕
    • Organizer
      第18回日本がん免疫学会総会
    • Place of Presentation
      松山
    • Year and Date
      2014-07-30 – 2014-08-01
    • Related Report
      2014 Annual Research Report
  • [Presentation] 高吸収性クルクミン併用による免疫抑制改善効果を介した免疫チェックポイント阻害療法の効果増強2014

    • Author(s)
      早川妙香、杉山重里、今泉厚、谷口智憲、河上裕
    • Organizer
      第18回日本がん免疫学会総会
    • Place of Presentation
      松山
    • Year and Date
      2014-07-30 – 2014-08-01
    • Related Report
      2014 Annual Research Report
  • [Presentation] 局所性Renin-Angiotensin systemの阻害による、がん関連線維芽細胞や骨髄系免疫細胞の制御を介したPD-1/PD-L1免疫チェックポイント阻害療法の効果増強2014

    • Author(s)
      中村謙太、谷口智憲、大村学、小林明日香、川村直、杉山重里、桜井敏晴、木庭幸子、奥山隆平、河上裕
    • Organizer
      第18回日本がん免疫学会総会
    • Place of Presentation
      松山
    • Year and Date
      2014-07-30 – 2014-08-01
    • Related Report
      2014 Annual Research Report
  • [Presentation] 悪性黒色腫に異所性に発現するHistatin-1は樹状細胞を抑制し、がん免疫回避に関与する2013

    • Author(s)
      谷口智憲、栗原智樹、後藤康文、伊藤有毅、守井賢二、小林明日香、西尾浩、住本秀敏、河上裕
    • Organizer
      第23回 日本樹状細胞研究会
    • Place of Presentation
      京都、京都、日本
    • Related Report
      2013 Research-status Report
  • [Presentation] 局所性Renin-Angiotensin systemは免疫抑制的がん微小環境の構築に関与する2013

    • Author(s)
      中村 謙太、谷口 智憲、大村 学、小林 明日香、川村 直、杉山 重里、桜井 敏晴、木庭 幸子、奥山 隆平、河上 裕
    • Organizer
      第17回 日本がん免疫学会総会
    • Place of Presentation
      宇部、山口、日本
    • Related Report
      2013 Research-status Report
  • [Presentation] ヒト卵巣明細胞腺癌に発現するHNF-1βは免疫抑制的がん微小環境の構築に関与する2013

    • Author(s)
      杉山重里、 谷口智憲、 川村直、 中村謙太、 大村学、 岩田卓、 藤田知信、 青木大輔、河上裕
    • Organizer
      第17回 日本がん免疫学会総会
    • Place of Presentation
      宇部、山口、日本
    • Related Report
      2013 Research-status Report
  • [Presentation] EGFR-TKIs (EGFR-tyrosin kinase inhibitors)は非小細胞肺癌と免疫担当細胞の両者に作用し抗腫瘍免疫応答を増強させる2013

    • Author(s)
      里見良輔、谷口智憲、 小林 明日香、副島研造、別役智子、河上裕
    • Organizer
      第17回 日本がん免疫学会総会
    • Place of Presentation
      宇部、山口、日本
    • Related Report
      2013 Research-status Report
  • [Presentation] EGFR-TKIs (EGFR-tyrosin kinase inhibitors) enhance anti-tumor immune responses in an EGFR independent manner2013

    • Author(s)
      Yaguchi T, Satomi R, Kobayashi A, Soejima K, Betsuyaku T, Kawakami Y
    • Organizer
      第72回 日本癌学会学術総会
    • Place of Presentation
      横浜、神奈川、日本
    • Related Report
      2013 Research-status Report
  • [Presentation] HNF-1β is an upstream molecule in immunosuppression by human ovarian clear cell carcinoma (OCCC)2013

    • Author(s)
      Sugiyama J, Yaguchi T, Kawamura N, Nakamura K, Ohmura G. Iwata T, Fujita T, Aoki D, Kawakami Y
    • Organizer
      第72回 日本癌学会学術総会
    • Place of Presentation
      横浜、神奈川、日本
    • Related Report
      2013 Research-status Report
  • [Presentation] Immunosuppressive roles of local renin–angiotensin system (RAS) in cancer microenvironments2013

    • Author(s)
      Nakamura K, Yaguchi T, Ohmura G. Kobayashi A Kawamura N, Sugiyama J, Sakurai T, Kiniwa Y, Okuyama R, Kawakami Y
    • Organizer
      第72回 日本癌学会学術総会
    • Place of Presentation
      横浜、神奈川、日本
    • Related Report
      2013 Research-status Report
  • [Presentation] Reversal of immunosuppression in ovarian cancer microenvironment by targeting NF-kB signal and its clinical application2013

    • Author(s)
      Nishio H, Yaguchi T, Sumimoto H, Umezawa K, Sugiyama J, Iwata T, Aoki D, Kawakami Y
    • Organizer
      第72回 日本癌学会学術総会
    • Place of Presentation
      横浜、神奈川、日本
    • Related Report
      2013 Research-status Report
  • [Presentation] Myosin 1bは頭頸部癌で過剰発現し、腫瘍細胞の浸潤・遊走・転移を促進する2013

    • Author(s)
      大村学、辻川敬裕、谷口智憲、川村直、中村謙太、杉山重里、三上修治、中野宏、島田剛敏、久育男、河上裕
    • Organizer
      第72回 日本癌学会学術総会
    • Place of Presentation
      横浜、神奈川、日本
    • Related Report
      2013 Research-status Report
  • [Presentation] NF-kBシグナルを標的とした卵巣癌局所における免疫抑制環境の改善と治療への応用2013

    • Author(s)
      岩田卓、田中京子、杉山重里、西尾浩、平尾薫丸、森定徹、早川妙香、谷口智憲、河上裕、青木大輔
    • Organizer
      第72回 日本癌学会学術総会
    • Place of Presentation
      横浜、神奈川、日本
    • Related Report
      2013 Research-status Report
  • [Presentation] Systemic administration of a highly absorptive form of curcumin reverses cancer-induced immunosuppression through inhibiting NF-kB and STAT32013

    • Author(s)
      Hayakawa T, Sugiyama J, Yaguchi T, Imaizumi A, Kawakami Y
    • Organizer
      第42回 日本免疫学会総会
    • Place of Presentation
      幕張、千葉、日本
    • Related Report
      2013 Research-status Report
  • [Presentation] Human PBMC transferred murine MHC class I/II deficient NOG mice are useful for analysis of human T/B cell responses2013

    • Author(s)
      Yaguchi T, Kobayashi A, Ka Y, Katano I, Ito M, Kawakami Y
    • Organizer
      第42回 日本免疫学会総会
    • Place of Presentation
      幕張、千葉、日本
    • Related Report
      2013 Research-status Report
  • [Presentation] MHC class I/II deficient NOG mice are useful for analysis of human T/B cell responses for human tumor immunology research2013

    • Author(s)
      Yaguchi T, Kobayashi A, Ka Y, Katano I, Ito M, Kawakami Y
    • Organizer
      SiTC 2013 28th annual meeting
    • Place of Presentation
      National Harbor, MD, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] がん微小環境における抑制性免疫細胞の誘導とその制御2013

    • Author(s)
      谷口 智憲、中村 謙太、杉山 重里、西尾 浩、川村 直、里見 良輔、河上 裕
    • Organizer
      第41回 臨床免疫学会総会
    • Place of Presentation
      下関、山口、日本
    • Related Report
      2013 Research-status Report
    • Invited

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi