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Comprehensive profiling of tumor immune microenvironment for effective personalized lung cancer vaccine

Research Project

Project/Area Number 17K10778
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Respiratory surgery
Research InstitutionThe University of Tokyo

Principal Investigator

Nagayama Kazuhiro  東京大学, 医学部附属病院, 助教 (00647935)

Co-Investigator(Kenkyū-buntansha) 中島 淳  東京大学, 医学部附属病院, 教授 (90188954)
佐藤 雅昭  東京大学, 医学部附属病院, 講師 (00623109)
安樂 真樹  東京大学, 医学部附属病院, 特任研究員 (70598557)
桑野 秀規  東京大学, 医学部附属病院, 助教 (60772324)
似鳥 純一  地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (40424486)
垣見 和宏  東京大学, 医学部附属病院, 特任教授 (80273358)
松下 博和  愛知県がんセンター(研究所), 腫瘍免疫制御TR分野, 分野長 (80597782)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords肺癌 / 遺伝子変異 / 次世代シーケンサー / ネオアンチゲン / 網羅的遺伝子解析 / TCGA / イムノグラム / 癌免疫療法 / 腫瘍内微小環境 / 多角的解析アルゴリズム / 治療効果予測
Outline of Final Research Achievements

For effective cancer therapy, it is important to choose optimal treatment combination for each patient, including personalized cancer vaccines, immunologic adjuvants, and checkpoint inhibitors. In our study, we developed an analytical pipeline to evaluate tumor immune microenvironment in each tumor using next-generation sequencing data. Then, we applied the pipeline to mouse lung cancer cell line LLC-1. Combination therapy of neoantigen vaccine and immune adjuvant elicited anti-tumor response in vivo.

Academic Significance and Societal Importance of the Research Achievements

癌に対する免疫治療の開発が近年盛んに行われているが、最適な癌治療を提供するには、患者毎に異なる癌免疫微小環境に対して、最適な免疫制御法の組み合わせを見つけなければならない。本研究では、次世代シーケンスデータを用いて腫瘍内免疫応答を多角的に評価する手法を、ヒト肺癌データを用いて開発した。その手法を用いてマウス肺癌細胞株に対する解析を行い、癌ワクチン、免疫アジュバント(補助剤)等を組み合わせてマウスに投与したところ、腫瘍の増殖が抑制された。本研究の意義は、癌免疫状態の評価法の開発と、有効な複合免疫治療の開発の双方に目を向けたという点である。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (21 results)

All 2020 2019 2018 2017

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 3 results) Presentation (13 results) (of which Int'l Joint Research: 2 results) Book (1 results)

  • [Journal Article] Clinical Application of Next-generation Sequencing for the Diagnosis of Lung Squamous Cell Carcinoma: Is It Primary or Secondary?2020

    • Author(s)
      Aizawa Hiroaki、Karasaki Takahiro、Nagayama Kazuhiro、Shinozaki-Ushiku Aya、Aburatani Hiroyuki、Mano Hiroyuki、Nakajima Jun
    • Journal Title

      Internal Medicine

      Volume: 59 Issue: 10 Pages: 1299-1302

    • DOI

      10.2169/internalmedicine.3682-19

    • NAID

      130007843218

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2020-05-15
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reduced Neoantigen Expression Revealed by Longitudinal Multiomics as a Possible Immune Evasion Mechanism in Glioma.2019

    • Author(s)
      Nejo T, Matsushita H, Karasaki T, Nomura M, Saito K, Tanaka S, Takayanagi S, Hana T, Takahashi S, Kitagawa Y, Koike T, Kobayashi Y, Nagae G, Yamamoto S, Ueda H, Tatsuno K, Narita Y, Nagane M, Ueki K, Nishikawa R, Aburatani H, Mukasa A, Saito N, Kakimi K.
    • Journal Title

      Cancer Immunol Res

      Volume: in press Issue: 7 Pages: 1148-1161

    • DOI

      10.1158/2326-6066.cir-18-0599

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Small lung tumor biopsy samples are feasible for high quality targeted next generation sequencing2019

    • Author(s)
      Kage Hidenori、Kohsaka Shinji、Shinozaki‐Ushiku Aya、Hiraishi Yoshihisa、Sato Jiro、Nagayama Kazuhiro、Ushiku Tetsuo、Takai Daiya、Nakajima Jun、Miyagawa Kiyoshi、Aburatani Hiroyuki、Mano Hiroyuki、Nagase Takahide
    • Journal Title

      Cancer Science

      Volume: 110 Issue: 8 Pages: 2652-2657

    • DOI

      10.1111/cas.14112

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Serum Antibody Against NY-ESO-1 and XAGE1 Antigens Potentially Predicts Clinical Responses to Anti?Programmed Cell Death-1 Therapy in NSCLC2019

    • Author(s)
      Ohue Yoshihiro、Kurose Koji、Karasaki Takahiro、Isobe Midori、Yamaoka Takaaki、Futami Junichiro、Irei Isao、Masuda Takeshi、Fukuda Masaaki、Kinoshita Akitoshi、Matsushita Hirokazu、Shimizu Katsuhiko、Nakata Masao、Hattori Noboru、Yamaguchi Hiroyuki、Fukuda Minoru、Nozawa Ryohei、Kakimi Kazuhiro、Oka Mikio
    • Journal Title

      Journal of Thoracic Oncology

      Volume: 14 Issue: 12 Pages: 2071-2083

    • DOI

      10.1016/j.jtho.2019.08.008

    • NAID

      120006796543

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 複合がん免疫療法とバイオマーカー2019

    • Author(s)
      唐崎隆弘、垣見和宏
    • Journal Title

      Bio Clinica

      Volume: 34 Pages: 35-39

    • Related Report
      2018 Research-status Report
  • [Journal Article] High CCR4 expression in the tumor microenvironment is a poor prognostic indicator in lung adenocarcinoma.2018

    • Author(s)
      Karasaki T, Qiang G, Anraku M, Sun Y, Shinozaki-Ushiku A, Sato E, Kashiwabara K, Nagayama K, Nitadori JI, Sato M, Murakawa T, Kakimi K, Fukayama M, Nakajima J.
    • Journal Title

      J Thorac Dis

      Volume: 10 Issue: 8 Pages: 4741-4750

    • DOI

      10.21037/jtd.2018.07.45

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] がん免疫療法とネオアンチゲン2017

    • Author(s)
      唐崎隆弘、垣見和宏
    • Journal Title

      がん分子標的治療

      Volume: 15 Pages: 72-76

    • Related Report
      2017 Research-status Report
  • [Presentation] The neoantigen landscape of murine lung cancer LLC1 model.2020

    • Author(s)
      孫長博
    • Organizer
      第17回日本免疫治療学会学術集会.
    • Related Report
      2019 Annual Research Report
  • [Presentation] Tumor Spread Through Air Spaces Is Associated with the Non-Inflamed Immune Microenvironment in Lung Squamous Cell Carcinoma.2019

    • Author(s)
      Karasaki T
    • Organizer
      ASLC 20th World Conference on Lung Cancer. Barcelona
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Spread through air spaces (STAS)を有する非小細胞肺癌に対する次世代シーケンスデータ解析.2019

    • Author(s)
      唐崎隆弘
    • Organizer
      第36回日本呼吸器外科学会学術集会.
    • Related Report
      2019 Annual Research Report
  • [Presentation] The neoantigen landscape of murine lung cancer LLC-1 model.2019

    • Author(s)
      孫長博
    • Organizer
      第23回日本がん免疫学会総会.
    • Related Report
      2019 Annual Research Report
  • [Presentation] 肺腺癌における tumor spread through air spaces (STAS)と癌免疫微小環境の関連性.2019

    • Author(s)
      唐崎隆弘
    • Organizer
      第60回日本肺癌学会学術集会.
    • Related Report
      2019 Annual Research Report
  • [Presentation] The neoantigen landscape of murine lung cancer LLC-1 model2018

    • Author(s)
      孫長博、長岡孝治、細井亮宏、垣見和宏
    • Organizer
      第16回日本免疫治療学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 肺腺癌におけるイムノゲノミクス解析2018

    • Author(s)
      唐崎隆弘、北野健太郎、長山和弘、似鳥純一、佐藤雅昭、安樂真樹、垣見和宏、中島淳
    • Organizer
      第35回日本呼吸器外科学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 肺腺癌におけるtumor mutational burden と癌免疫微小環境の関連性2018

    • Author(s)
      唐崎隆弘、長山和弘、垣見和宏、中島淳
    • Organizer
      第59回日本肺癌学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Difference of tumor mutational burden is associated with distinct immune microenviroment in the T cell-inflamed lung adenocarcinoma2018

    • Author(s)
      Karasaki T, Kitano K, Nagayama K, Nitadori JI, Sato M, Anraku M, Kakimi K, Nakajima J
    • Organizer
      IASLC 19th World Conference on Lung Cancer
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Assessment of cancer immunity status in each patient using immunoguram.2017

    • Author(s)
      Karasaki T, Nagayama K, Fukumoto K, Kitano K, Nitadori J, Sato M, Anraku M, Hosoi A, Matsushita H, Kakimi K, Nakajima J.
    • Organizer
      18th World Conference on Lung Cancer
    • Related Report
      2017 Research-status Report
  • [Presentation] イムノグラムを用いた個別化癌治療の最適化2017

    • Author(s)
      唐崎 隆弘, 福元 健人, 松下 博和, 長山 和弘, 中島 淳, 垣見 和宏
    • Organizer
      第76回 日本癌学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Immunogramを用いた肺癌免疫治療の最適化2017

    • Author(s)
      唐崎 隆弘, 長山 和弘, 垣見 和宏, 中島 淳
    • Organizer
      第34回 日本呼吸器外科学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] イムノグラムを用いた肺癌治療の最適化2017

    • Author(s)
      唐崎 隆弘. 長山 和弘, 中尾 啓太, 乾 雅人, 長野 匡晃, 川島 光明, 桧山 紀子, 桑野 秀規, 似鳥 純一, 佐藤 雅昭, 安樂 真樹, 松下 博和, 垣見 和宏, 中島 淳
    • Organizer
      第117回 日本外科学会定期学術集会
    • Related Report
      2017 Research-status Report
  • [Book] 複合がん免疫療法とバイオマーカー2019

    • Author(s)
      唐崎隆弘、垣見和宏
    • Publisher
      北降館
    • Related Report
      2019 Annual Research Report

URL: 

Published: 2017-04-28   Modified: 2021-02-19  

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