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Analysis of intratumoral immune response in gastric and esophageal cancer for optimal combination immunotherapy

Research Project

Project/Area Number 17K10578
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

Yagki Koichi  東京大学, 医学部附属病院, 助教 (90422310)

Co-Investigator(Kenkyū-buntansha) 瀬戸 泰之  東京大学, 医学部附属病院, 教授 (00260498)
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
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
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: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords食道癌 / 胃癌 / イムノグラム / 腫瘍免疫 / 免疫応答 / 複合的免疫治療 / ネオアンチゲン / バイオマーカー / 免疫治療
Outline of Final Research Achievements

We collected tumor and adjacent tissue from 50 gastric cancer patients and 58 esophageal cancer patients. We performed whole-exome and RNA sequencing, and flow cytometry in cancer of 29 gastric cancer patients. We have developed immunogram based on RNA-Seq using 9 selected gene sets. By integrating them, we generated an immunogram for each patient. Immunograms of the 29 patients differ from patient to patient. These results demonstrate that the anti-tumor immune response in gastric cancer is heterogeneous. The hierarchical clustering of Immunogram of these patients resulted in 4 novel immunological subtypes. Hot tumors were further divided into 2 subtypes, between which the functional status of T-cells was different. This novel immunological subtypes could be useful for improving the efficacy of current immunotherapies or developing novel combination immunotherapies. We are analysing for esophageal cancer.

Academic Significance and Societal Importance of the Research Achievements

本研究では、胃癌症例において、手術検体と末梢血検体を用いて、次世代シークエンス、フローサイトメトリー、液性因子解析を行い、腫瘍内免疫応答を多層的に解析し、がん免疫サイクルの概念に基づく「イムノグラム」により腫瘍内免疫応答を視覚的に表現した。その結果、胃癌患者個々の腫瘍内免疫応答はそれぞれ異なっていることが判明し、クラスター解析から胃癌が免疫学的に4つに分類された。この分類では、胃癌における腫瘍内免疫応答が特徴づけられており、腫瘍内免疫応答の評価に有用であり、さらに、腫瘍内免疫応答の評価に基づく個別化免疫治療や新規の複合的免疫治療の開発に有用であると考えられる。

Report

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

    (22 results)

All 2020 2019 2018 2017

All Journal Article (10 results) (of which Peer Reviewed: 10 results,  Open Access: 7 results) Presentation (12 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] Pre- and post-operative low prognostic nutritional index influences survival in older patients with gastric carcinoma2020

    • Author(s)
      Sugawara Kotaro、Aikou Susumu、Yajima Sho、Uemura Yukari、Okumura Yasuhiro、Nishida Masato、Yagi Koichi、Yamashita Hiroharu、Seto Yasuyuki
    • Journal Title

      Journal of Geriatric Oncology

      Volume: Epub ahead of print Issue: 6 Pages: 0-0

    • DOI

      10.1016/j.jgo.2020.02.007

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Perioperative fluid dynamics evaluated by bioelectrical impedance analysis predict infectious surgical complications after esophagectomy2019

    • Author(s)
      Oya Shuichiro、Yamashita Hiroharu、Iwata Ryohei、Kawasaki Koichiro、Tanabe Asami、Yagi Koichi、Aikou Susumu、Seto Yasuyuki
    • Journal Title

      BMC Surgery

      Volume: 19 Issue: 1 Pages: 0-0

    • DOI

      10.1186/s12893-019-0652-z

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pregnancy, delivery, and breastfeeding after total gastrectomy for gastric cancer: a case report2018

    • Author(s)
      Higashizono Kazuya、Nomura Sachiyo、Yagi Koichi、Aikou Susumu、Nishida Masato、Yamashita Hiroharu、Seto Yasuyuki
    • Journal Title

      World Journal of Surgical Oncology

      Volume: 16 Issue: 1 Pages: 1-5

    • DOI

      10.1186/s12957-018-1531-2

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mediastinoscopic view of the bronchial arteries in a series of surgical cases evaluated with three-dimensional computed tomography2018

    • Author(s)
      Mori Kazuhiko、Ino Kenji、Yoshimura Shuntaro、Aikou Susumu、Yagi Koichi、Nishida Masato、Mitsui Takashi、Okumura Yasuhiro、Yamagata Yukinori、Yamashita Hiroharu、Nomura Sachiyo、Seto Yasuyuki
    • Journal Title

      Esophagus

      Volume: 15 Issue: 3 Pages: 173-179

    • DOI

      10.1007/s10388-018-0609-9

    • NAID

      40021587952

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Quality of life after robot-assisted transmediastinal radical surgery for esophageal cancer2018

    • Author(s)
      Yoshimura Shuntaro、Mori Kazuhiko、Yamagata Yukinori、Aikou Susumu、Yagi Koichi、Nishida Masato、Yamashita Hiroharu、Nomura Sachiyo、Seto Yasuyuki
    • Journal Title

      Surgical Endoscopy

      Volume: 32 Issue: 5 Pages: 2249-2254

    • DOI

      10.1007/s00464-017-5918-x

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Non-linear association between long-term outcome and preoperative neutrophil-to-lymphocyte ratio in patients undergoing curative resection for gastric cancer: a retrospective analysis of 1335 cases in a tetrachotomous manner2018

    • Author(s)
      Urabe Masayuki、Yamashita Hiroharu、Uemura Yukari、Tanabe Asami、Yagi Koichi、Aikou Susumu、Seto Yasuyuki
    • Journal Title

      Japanese Journal of Clinical Oncology

      Volume: 48 Issue: 4 Pages: 343-349

    • DOI

      10.1093/jjco/hyy005

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A surgical case of radiotherapy induced esophageal perforation accompanying pyogenic spondylodiscitis: a case report2017

    • Author(s)
      Yoshimura Shuntaro、Mori Kazuhiko、Kawasaki Koichiro、Tanabe Asami、Aikou Susumu、Yagi Koichi、Nishida Masato、Yamashita Hiroharu、Nomura Sachiyo、Fukushima Masayoshi、Yamashita Hideomi、Yamauchi Yasuhiro、Seto Yasuyuki
    • Journal Title

      Surgical Case Reports

      Volume: 3 Issue: 1 Pages: 1-5

    • DOI

      10.1186/s40792-017-0368-1

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] DNA methylation epigenotype and clinical features of NRAS-mutation(+) colorectal cancer.2017

    • Author(s)
      Takane K. Akagi K. Fukuyo M. Yagi K. Takayama T. Kaneda A.
    • Journal Title

      Cancer Med

      Volume: 印刷中 Issue: 5 Pages: 1023-1035

    • DOI

      10.1002/cam4.1061

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] How should we define the no. 3b lesser curvature lymph node?2017

    • Author(s)
      Yamashita Hiroharu、Yagi Koichi、Seto Yasuyuki
    • Journal Title

      Gastric Cancer

      Volume: 20 Issue: 3 Pages: 558-559

    • DOI

      10.1007/s10120-016-0638-9

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Efficacy of trastuzumab beyond progression as second-line chemotherapy for HER2-positive advanced gastric cancer2017

    • Author(s)
      Sato Yasuyoshi、Yamashita Hiroharu、Yagi Koichi、Aikou Susumu、Nishida Masato、Takenaka Yoshiharu、Nomura Sachiyo、Seto Yasuyuki
    • Journal Title

      Gastrointestinal Cancer: Targets and Therapy

      Volume: Volume 7 Pages: 39-45

    • DOI

      10.2147/gictt.s145634

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 胃癌における腫瘍内免疫応答の解析2020

    • Author(s)
      佐藤 靖祥,八木浩一,山下裕玄,小林由香利,藤枝奈緒,長岡孝治,細井亮宏,垣見和宏,瀬戸泰之
    • Organizer
      第24回日本がん分子標的治療学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Abscopal effect in a patient with gastric cancer followed by nivolumab and radiotherapy: serum immune response analysis2019

    • Author(s)
      Yasuyoshi Sato, Hiroharu Yamashita, Koichi Yagi, Sachiyo Nomura, Hideomi Yamashita, Nao Fujieda, Junichiro Futami, Kazuhiro Kakimi, Yasuyuki Seto
    • Organizer
      2019 Annual Meeting of Japanese Society of Medical Oncology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 当科における75歳以上高齢者食道癌患者に対する治療成績の検討2018

    • Author(s)
      八木浩一
    • Organizer
      第72回 日本食道学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] P0CY1胃癌に対する治療方針-切除先行か化療先行か2018

    • Author(s)
      八木浩一
    • Organizer
      第118回日本外科学会定期学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] ロボット支援下根治的非開胸食道切除の現状、課題、展望2018

    • Author(s)
      八木浩一
    • Organizer
      第73回日本消化器外科学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] A Two-Stage Operation Using a Free Jejunal Flap for Gastrectomized Esophageal Cancer2018

    • Author(s)
      八木浩一
    • Organizer
      第16回国際食道学会
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Autologous tumor lysate-pulsed dendritic cell vaccination therapy after resection of stage IIA (T2N0, T3N0) esophageal cancer: An analysis of immunological responses2018

    • Author(s)
      Yasuyoshi Sato, Koichi Yagi, Kazuhiko Mori, Hirokazu Matsushita, Kazuhiro Kakimi and Yasuyuki Seto
    • Organizer
      The ASCO-SITC Clinical Immuno-Oncology Symposium
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] ESD非治癒切除胃癌に対する追加切除例からみるリンパ節転移と癌局所遺残の検討2017

    • Author(s)
      八木 浩一, 山下 裕玄, 瀬戸 泰之
    • Organizer
      日本肝臓学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 高齢者食道癌に対する食道亜全摘術の治療成績2017

    • Author(s)
      八木 浩一, 西田 正人, 三ツ井 崇司, 愛甲 丞, 山下 裕玄, 野村 幸世, 森 和彦, 瀬戸 泰之
    • Organizer
      日本食道学会
    • Related Report
      2017 Research-status Report
  • [Presentation] ESD非治癒切除胃癌に対する追加切除例からみるリンパ節転移と癌局所遺残の検討2017

    • Author(s)
      八木 浩一, 山下 裕玄, 瀬戸 泰之
    • Organizer
      日本消化器がん検診学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 食道切除後再建法の工夫と成績 胃切除後食道癌に対する遊離空腸を用いた再建方法2017

    • Author(s)
      八木 浩一, 西田 正人, 三ツ井 崇司, 愛甲 丞, 山下 裕玄, 野村 幸世, 森 和彦, 瀬戸 泰之
    • Organizer
      日本消化器外科学会
    • Related Report
      2017 Research-status Report
  • [Presentation] ESD非治癒切除胃癌に対する追加切除例からみるリンパ節転移と癌局所遺残の検討2017

    • Author(s)
      八木 浩一, 山下 裕玄, 瀬戸 泰之
    • Organizer
      日本消化器内視鏡学会
    • Related Report
      2017 Research-status Report

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

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