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Immune escape mediated by the EGFR-derived signal: From Mechanism to Therapy

Research Project

Project/Area Number 15K09237
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionIwate Medical University (2017)
Miyagi Prefectural Hospital Organization Miyagi Cancer Center (2015-2016)

Principal Investigator

Mamondo Makoto  岩手医科大学, 医学部, 教授 (40344676)

Co-Investigator(Kenkyū-buntansha) 田中 伸幸  地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), がん先進治療開発研究部, 部長 (60280872)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords非小細胞肺癌 / EGFR / 分子細胞腫瘍学 / 肺癌 / モデルマウス / 分子細胞呼吸器学 / 免疫チェックポイント
Outline of Final Research Achievements

Immune checkpoint inhibitors targeting PD-L1 and PD-1 often show synergistic effects on NSCLCs. To elucidate the role of EGFR-mediated signal on lung tumor immunology, LLC cells were examined for the immune modulator expression. Although LAG-3 and B7-H3 expression was negative, a fair amount of PD-L1 was detected. We then established PD-L1 knockout cells and implanted into syngeneic mice, but TIL infiltration was relatively low. To increase TIL infiltration we introduced CTIIA, and succeeded in MHC up-regulation.

Report

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

Research Products

(12 results)

All 2018 2017 2016 2015

All Journal Article (10 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 10 results,  Open Access: 7 results,  Acknowledgement Compliant: 5 results) Presentation (2 results)

  • [Journal Article] Deficiency of protein-L-isoaspartate (D-aspartate) <i>O</i>-methyl-transferase expression under endoplasmic reticulum stress promotes epithelial mesenchymal transition in lung adenocarcinoma2018

    • Author(s)
      Yamashita Masahiro、Ogasawara Masahito、Kawasaki Yasushi、Niisato Miyuki、Saito Heisuke、Kasai Shuya、Maesawa Chihaya、Maemondo Makoto、Yamauchi Kohei
    • Journal Title

      Oncotarget

      Volume: 9 Pages: 13287-13300

    • DOI

      10.18632/oncotarget.24324

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] PKM1 Confers Metabolic Advantages and Promotes Cell-Autonomous Tumor Cell Growth.2018

    • Author(s)
      M Morita, T Sato, M Nomura, Y Sakamoto, Y Inoue, R Tanaka, S Ito, K Kurosawa, K Yamaguchi, Y Sugiura, H Takizaki, Y Yamashita, R Katakura, I Sato, Y Okada, H Watanabe, G Kondoh, et al.
    • Journal Title

      Cancer Cell

      Volume: 12 Pages: 355-367

    • DOI

      10.1016/j.ccell.2018.02.004

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Updated survival outcomes of NEJ005/TCOG0902: a randomised phase II study of concurrent versus sequential alternating gefitinib and chemotherapy in previously untreated non-small cell lung cancer with sensitive EGFR mutations.2018

    • Author(s)
      Oizumi S, Sugawara S, Minato K, Harada T, Inoue A, Fujita Y, Maemondo M, Watanabe S, Ito K, Gemma A, Demura Y, Fukumoto S, Isobe H, Kinoshita I, Morita S, Kobayashi K, Hagiwara K, Aiba K, Nukiwa T.
    • Journal Title

      ESMO Open

      Volume: 3(2)

    • DOI

      10.1136/esmoopen-2017-000313

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Distinct Profiles of CD163-Positive Macrophages in Idiopathic Interstitial Pneumonias2018

    • Author(s)
      Yamashita M, Saito R, Yasuhira S, Fukuda Y, Sasamo H, Sugai T, Yamauchi K, Maemondo M
    • Journal Title

      J Immunol Res.

      Volume: 2018 Pages: 1436236-1436236

    • DOI

      10.1155/2018/1436236

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Randomized controlled trial of S-1 versus docetaxel in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy (East Asia S-1 Trial in Lung Cancer)2017

    • Author(s)
      Nokihara H
    • Journal Title

      Ann Oncol

      Volume: 28 Pages: 2698-2706

    • DOI

      10.1093/annonc/mdx419

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] EGFR Mutation Analysis of Circulating Tumor DNA Using an Improved PNA-LNA PCR Clamp Method2016

    • Author(s)
      Watanabe K, Fukuhara T, Tsukita Y, Morita M, Suzuki A, Tanaka N, Terasaki H, Nukiwa T, Maemondo M
    • Journal Title

      Can Respir J.

      Volume: 5297329 Pages: 5297329-5297329

    • DOI

      10.1155/2016/5297329

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Randomized phase II trial comparing amrubicin with re-challenge of platinum doublet in patients with sensitive-relapsed small-cell lung cancer: North Japan Lung Cancer Study Group trial 07022015

    • Author(s)
      .Inoue A, Sugawara S, Maemondo M, Mori Y, Oizumi S, Harada M, Taima K, Morikawa N, Ishida T, Kinoshita I, Watanabe H, Suzuki T, Nakagawa T, Saito R, Nukiwa T
    • Journal Title

      Lung Cancer

      Volume: 89 Pages: 61-5

    • DOI

      10.1016/j.lungcan.2015.04.012

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Loss of protein phosphatase 6 in mouse keratinocytes increases susceptibility to ultraviolet-B-induced carcinogenesis.2015

    • Author(s)
      Kato H, Kurosawa K, Inoue Y, Tanuma N, Momoi Y, Hayashi K, Ogoh H, Nomura M, Sakayori M, Kakugawa Y, Yamashita Y, Miura K, Maemondo M, Katakura R, Ito S, Sato M, Sato I, Chiba N, Watanabe T, Shima H.
    • Journal Title

      Cancer letters

      Volume: 365 Pages: 223-228

    • DOI

      10.1016/j.canlet.2015.05.022

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Factors associated with a poor response to gefitinib in the NEJ002 study: Smoking and the L858R mutation.2015

    • Author(s)
      Fukuhara T, Yoshizawa H et al.
    • Journal Title

      Lung Cancer

      Volume: 88 Pages: 181-186

    • DOI

      10.1016/j.lungcan.2015.02.004

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The role of smoking status on the progression-free survival of non-small-cell lung cancer patients harboring activating epidermal growth factor (EGFR) mutations receiving first-line EGFR tyrosine kinase inhibitor: a meta-analysis of prospective randomized trials.2015

    • Author(s)
      Hasegawa Y, Ando M, Maemondo M, Yamamoto S, Isa S, Saka H, Kubo A, Kawaguchi T, Takada M, Rosell R, Kurata T, Ou SH.
    • Journal Title

      Oncologst

      Volume: 20 Pages: 307-315

    • DOI

      10.1634/theoncologist.2014-0285

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] alectinib耐性後にc-Met遺伝子増幅を来しcrizotinibが奏効したALK融合遺伝子陽性肺腺癌の一例,2015

    • Author(s)
      渡邉香奈、突田容子、盛田麻美、鈴木綾、福原達朗、玉井恵一、片山量平、前門戸任
    • Organizer
      第56回日本肺癌学会学術集会
    • Place of Presentation
      横浜市
    • Year and Date
      2015-11-26
    • Related Report
      2015 Research-status Report
  • [Presentation] 高感度EGFR遺伝子変異解析を用いた非小細胞肺癌血漿中循環DNAの測定2015

    • Author(s)
      渡邉香奈、福原達郎、突田容子、盛田麻美、鈴木綾、寺崎浩司、前門戸任
    • Organizer
      第55回日本呼吸器学会学術講演会
    • Place of Presentation
      東京
    • Year and Date
      2015-04-17
    • Related Report
      2015 Research-status Report

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

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