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Establishment of combined cancer immunotherapy using neoantigen-induced mouse model

Research Project

Project/Area Number 18K16771
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 56040:Obstetrics and gynecology-related
Research InstitutionShimane University

Principal Investigator

Ishibashi Tomoka  島根大学, 学術研究院医学・看護学系, 助教 (40643648)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords癌免疫 / 癌免疫療法 / PD-1/PD-L1 / 複合的癌免疫療法 / 婦人科腫瘍
Outline of Final Research Achievements

We reported that PD-1/PD-L1 inhibitors might be effective in patients with MSI-high endometrial cancers, and that MSI-high will be a potential biomarker for PD-1/PD-L1 inhibitors. In addition, we also reported that MSI-high is frequently observed in dedifferentiated endometrial cancers, and in undifferentiated cancer portions, the effect of immune checkpoint inhibitors can be expected. We speculated that combined treatment with anti-cancer drug and immune check point inhibitors may be effective for dedifferentiated endometrial cancers. Furthermore, we concluded that immune checkpoint inhibitors may be effective in patients with cervical adenocarcinoma with high PD-L1 expression. On the other hand, according to our genetic analysis in ovarian cancers, the frequency of MSI-high is estimated to be about 5%. Therefore, combined immune cancer treatment in combination with other anti-cancer drugs should be needed for patients with ovarian cancers.

Academic Significance and Societal Importance of the Research Achievements

卵巣癌では既に免疫チェックポイント阻害薬の奏功が報告されたが、治療効果が特に期待される集団については検討されていなかった。MSIまたはPOLE変異が関連する癌はmutation burden richと考えられるが、当科の研究では卵巣癌におけるMSI-highの頻度は5%程度であった。卵巣癌に対する免疫チェックポイント阻害薬の効果が期待されたが、他の薬剤と併用する複合的がん療法の必要性が示唆された。卵巣癌におけるこれらmutation burden richな腫瘍と免疫チェックポイント阻害薬の効果を検討することは、今後個別化した治療を選択する上で重要であり、今後臨床応用の可能性がある。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (40 results)

All 2021 2020 2019 2018

All Journal Article (16 results) (of which Int'l Joint Research: 11 results,  Peer Reviewed: 16 results,  Open Access: 16 results) Presentation (23 results) Book (1 results)

  • [Journal Article] Whole-Exome Sequencing of Rare Site Endometriosis-Associated Cancer.2021

    • Author(s)
      Kurose S, Nakayama K, Razia S, Ishikawa M, Ishibashi T, Yamashita H, Sato S, Sakiyama A, Yoshioka S, Kobayachi M, Nakayama S, Otsuki Y, Ishikawa N, Kyo S.
    • Journal Title

      Diseases (Basel, Switzerland)

      Volume: 9 Issue: 1 Pages: 14-14

    • DOI

      10.3390/diseases9010014

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] High PD-1 expression level is associated with an unfavorable prognosis in patients with cervical adenocarcinoma.2020

    • Author(s)
      Masako Ishikawa, Kentaro Nakayama, Kohei Nakamura, Hitomi Yamashita, Tomoka Ishibashi, Toshiko Minamoto, Kouji Iida, Sultana Razia, Noriyoshi Ishikawa, Satoru Nakayama, Yoshiro Otsuki, Satoru Kyo
    • Journal Title

      Archives of gynecology and obstetrics

      Volume: 302 Issue: 1 Pages: 209-218

    • DOI

      10.1007/s00404-020-05589-0

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prognostic Value of Peripheral Blood Lymphocyte Telomere Length in Gynecologic Malignant Tumors.2020

    • Author(s)
      Shanta K, Nakayama K, Ishikawa M, Ishibashi T, Yamashita H, Sato S, Sasamori H, Sawada K, Kurose S, Mahmud HM, Razia S, Iida K, Ishikawa N, Kyo S
    • Journal Title

      Cancers

      Volume: 12 Issue: 6 Pages: 1469-1469

    • DOI

      10.3390/cancers12061469

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mucinous borderline ovarian tumors with BRAF V600E mutation may have low risk for progression to invasive carcinomas2020

    • Author(s)
      hnishi K, Nakayama K, Ishikawa M, Ishibashi T, Yamashita H, Nakamura K, Minamoto T, Iida K, Razia S, Ishikawa N, Kyo S.
    • Journal Title

      Arch Gynecol Obstet

      Volume: 302 Issue: 2 Pages: 487-495

    • DOI

      10.1007/s00404-020-05638-8

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The fallopian tube as origin of ovarian cancer: Change of diagnostic and preventive strategies.2020

    • Author(s)
      Satoru Kyo, Noriyoshi Ishikawa, Kohei Nakamura, Kentaro Nakayama
    • Journal Title

      Cancer medicine

      Volume: 9 Issue: 2 Pages: 421-431

    • DOI

      10.1002/cam4.2725

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] High Frequency of PIK3CA Mutations in Low-Grade Serous Ovarian Carcinomas of Japanese Patients. Diagnostics (Basel). 2019;27;10(1). pii: E13.2019

    • Author(s)
      Ishibashi T, Nakayama K, Razia S, Ishikawa M, Nakamura K, Yamashita H, Dey P, Iida K, Kurioka H, Nakayama S, Otsuki Y, Ishikawa N, Kyo S.
    • Journal Title

      Diagnostics (Basel).

      Volume: 27;10(1) Issue: 1 Pages: 13-13

    • DOI

      10.3390/diagnostics10010013

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Sarcopenic Factors May Have No Impact on Outcomes in Ovarian Cancer Patients2019

    • Author(s)
      Nakayama Naomi、Nakayama Kentaro、Nakamura Kohei、Razia Sultana、Kyo Satoru
    • Journal Title

      Diagnostics

      Volume: 9 Issue: 4 Pages: 206-206

    • DOI

      10.3390/diagnostics9040206

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Relationship between Microsatellite Instability, Immune Cells Infiltration, and Expression of Immune Checkpoint Molecules in Ovarian Carcinoma: Immunotherapeutic Strategies for the Future.2019

    • Author(s)
      Hitomi Yamashita, Kentaro Nakayama, Masako Ishikawa, Tomoka Ishibashi, Kohei Nakamura, Kiyoka Sawada, Yuki Yoshimura, Nagisa Tatsumi, Sonomi Kurose, Toshiko Minamoto, Kouji Iida, Sultana Razia, Noriyoshi Ishikawa, Satoru Ky
    • Journal Title

      International journal of molecular sciences

      Volume: 20 Issue: 20 Pages: 1-1

    • DOI

      10.3390/ijms20205129

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Clinicopathological and biological analysis of PIK3CA mutation and amplification in cervical carcinomas.2019

    • Author(s)
      Sultana Razia, Kentaro Nakayama, Kohei Nakamura, Tomoka Ishibashi, Masako Ishikawa, Toshiko Minamoto, Kouji Iida, Yoshiro Otsuki, Satoru Nakayama, Noriyoshi Ishikawa, Satoru Kyo
    • Journal Title

      Experimental and therapeutic medicine

      Volume: 18 Pages: 2278-2284

    • DOI

      10.3892/etm.2019.7771

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dedifferentiated Endometrial Carcinoma Could be A Target for Immune Checkpoint Inhibitors (Anti PD-1/PD-L1 Antibodies).2019

    • Author(s)
      Ruriko Ono, Kentaro Nakayama, Kohei Nakamura, Hitomi Yamashita, Tomoka Ishibashi, Masako Ishikawa, Toshiko Minamoto, Sultana Razia, Noriyoshi Ishikawa, Yoshiro Otsuki, Satoru Nakayama, Hideyuki Onuma, Hiroko Kurioka, Satoru Kyo
    • Journal Title

      International journal of molecular sciences

      Volume: 20 Issue: 15 Pages: 1-1

    • DOI

      10.3390/ijms20153744

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] High frequency of POLE mutations in synchronous endometrial and ovarian carcinoma.2018

    • Author(s)
      Ishikawa M, Nakayama K*, Nakamura K, Ono R, Yamashita H, Ishibashi T, Minamoto T, Iida K, Razia S, Ishikawa N, Kyo S.
    • Journal Title

      Hum Pathol

      Volume: 18 Pages: 30424-30426

    • DOI

      10.1016/j.humpath.2018.11.001

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Genetic analysis and phosphoinositide???3?kinase/protein kinase B signaling pathway status in ovarian endometrioid borderline tumor samples2018

    • Author(s)
      Nakamura Kohei、Nakayama Kentaro、Ishikawa Masako、Minamoto Toshiko、Ishibashi Tomoka、Sato Emi、Sanuki Kaori、Yamashita Hitomi、Ono Ruriko、Iida Kouji、Sultana Razia、Hossain Mohammad、Ishikawa Noriyoshi、Kyo Satoru
    • Journal Title

      Oncology Letters

      Volume: 16 Pages: 189-194

    • DOI

      10.3892/ol.2018.8626

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ARID1B as a Potential Therapeutic Target for ARID1A-Mutant Ovarian Clear Cell Carcinoma2018

    • Author(s)
      Sato Emi、Nakayama Kentaro、Razia Sultana、Nakamura Kohei、Ishikawa Masako、Minamoto Toshiko、Ishibashi Tomoka、Yamashita Hitomi、Iida Kouji、Kyo Satoru
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 19 Issue: 6 Pages: 1710-1710

    • DOI

      10.3390/ijms19061710

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Preoperative tumor size is associated with deep myometrial invasion and lymph node metastases and is a negative prognostic indicator for patients with endometrial carcinoma2018

    • Author(s)
      Nakamura Kohei、Nakayama Kentaro、Ishikawa Noriyoshi、Minamoto Toshiko、Ishibashi Tomoka、Ohnishi Kaori、Yamashita Hitomi、Ono Ruriko、Sasamori Hiroki、Razia Sultana、Hossain Mohammad Mahmud、Kamrunnahar Shanta、Ishikawa Masako、Kyo Satoru
    • Journal Title

      Oncotarget

      Volume: 9 Issue: 33 Pages: 23164-23172

    • DOI

      10.18632/oncotarget.25248

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cancer-related transcription regulator protein NAC1 forms a protein complex with CARM1 for ovarian cancer progression.2018

    • Author(s)
      Nakayama N, Sakashita G, Nariai Y, Kato H, Sinmyozu K, Nakayama JI, Kyo S, Urano T, Nakayama K.
    • Journal Title

      Oncotarget

      Volume: 9 Issue: 47 Pages: 28408-28420

    • DOI

      10.18632/oncotarget.25400

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lynch Syndrome-Related Clear Cell Carcinoma of the Cervix: A Case Report2018

    • Author(s)
      Nakamura Kohei、Nakayama Kentaro、Minamoto Toshiko、Ishibashi Tomoka、Ohnishi Kaori、Yamashita Hitomi、Ono Ruriko、Sasamori Hiroki、Razia Sultana、Hossain Mohammad Mahmud、Kamrunnahar Shanta、Ishikawa Masako、Ishikawa Noriyoshi、Kyo Satoru
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 19 Issue: 4 Pages: 979-979

    • DOI

      10.3390/ijms19040979

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Relationship among microsatellite instability, immune cells infiltration, and expression of immune checkpoint molecules in ovarian carcinoma: immunotherapeutic strategies for the future2020

    • Author(s)
      Yamashita H, Nakayama K, Ishibashi T, Kyo S, et al
    • Organizer
      第72回日本産科婦人科学会学術講演会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Clinical sequence for refractory cancers: A single-center analysis of 48 cases2020

    • Author(s)
      Tatsumi N, Nakayama K, Ishibashi T, Kyo S, et al
    • Organizer
      第72回日本産科婦人科学会学術講演会
    • Related Report
      2020 Annual Research Report
  • [Presentation] High PD-1 expression level is associated with an unfavorable prognosis in patients with cervical adenocarcinoma2020

    • Author(s)
      Ishikawa M, Nakayama K, Ishibashi T, Kyo S, et al
    • Organizer
      第72回日本産科婦人科学会学術講演会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Establish a novel in vitro model of deep infiltering endometriosis for understanding its biology and molecular pathogenesis2020

    • Author(s)
      Hossain M, Nakayama K, Ishibashi T, Kyo S, et al
    • Organizer
      第72回日本産科婦人科学会学術講演会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Prognostic value of peripheral blood lymphocyte telomere length in gynecologic malignancies2020

    • Author(s)
      Shanta K, Nakayama K, Ishibashi T, Kyo S, et al
    • Organizer
      第72回日本産科婦人科学会学術講演会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 稀少部位子宮内膜症の悪性転化例の発癌機構解析2020

    • Author(s)
      黒瀬苑水、中山健太郎、石橋朋佳、京哲、その他
    • Organizer
      第19回日本婦人科がん分子標的研究会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 網羅的がん遺伝子検査による、がんプレシジョンメディスンの実践2019

    • Author(s)
      吉村由紀、中山健太郎、澤田希代加、山下瞳、中村康平、石橋朋佳、石川雅子、京哲
    • Organizer
      第71回日本産科婦人科学会学術講演会
    • Related Report
      2019 Research-status Report
  • [Presentation] Immune checkpoint Inhibitors (anti PD-1/PD-L1 antibody) could be effective in dedifferentiated endometrial carcinoma.2019

    • Author(s)
      Ono R, Nakayama K, Ishibashi T, Ishikawa M, Nakamura K, Nakamura A, Sawada K, Yamashita H, Yoshimura Y, Kyo S.
    • Organizer
      第71回日本産科婦人科学会学術講演会
    • Related Report
      2019 Research-status Report
  • [Presentation] Origin of Serous cystadenoma.2019

    • Author(s)
      中村康平、中山健太郎、澤田希代加、吉村由紀、山下瞳、石橋朋佳、石川雅子、京哲
    • Organizer
      第71回日本産科婦人科学会学術講演会
    • Related Report
      2019 Research-status Report
  • [Presentation] Mutation analysis of Low grade serous ovarian carcinoma, serous borderline tumor and ovarian serous cystadenoma in Japanese population.2019

    • Author(s)
      Ishibashi T, Nakayama K, Ishikawa M, Nakamura K, Sawada K, Yamashita H, Yoshimura Y, Iida K, Sultana R, Kyo S.
    • Organizer
      第71回日本産科婦人科学会学術講演会
    • Related Report
      2019 Research-status Report
  • [Presentation] 低悪性度漿液性癌の発現過程におけるOSEの卵管上皮化成について2019

    • Author(s)
      中村康平、中山健太郎、吉村由紀、澤田希代加、山下瞳、石橋朋佳、石川雅子、京哲
    • Organizer
      第61回日本婦人科腫瘍学会学術講演会
    • Related Report
      2019 Research-status Report
  • [Presentation] がん遺伝子パネル検査におけるGenestic heterogeneityへの対応2019

    • Author(s)
      吉村由紀、中山健太郎、中村康平、澤田希代加、山下瞳、石橋朋佳、石川雅子、京哲
    • Organizer
      第6回中日本産婦人科セミナー
    • Related Report
      2019 Research-status Report
  • [Presentation] クリニカルシークエンスでの問題点~Genetic heterogeneityにいかに対応していくか~2019

    • Author(s)
      吉村由紀、中山健太郎、中村康平、澤田希代加、山下瞳、石橋朋佳、石川雅子、京哲
    • Organizer
      第18回日本婦人かがん分子標的研究会
    • Related Report
      2019 Research-status Report
  • [Presentation] Genetic heterogeneityがprecision medicineに与える影響~サンプリング部位の選択に対する警鐘~2019

    • Author(s)
      吉村由紀、中山健太郎、中村康平、澤田希代加、山下瞳、石橋朋佳、石川雅子、京哲
    • Organizer
      第61回日本婦人科腫瘍学会学術講演会
    • Related Report
      2019 Research-status Report
  • [Presentation] 子宮頸部腺癌における免疫チェックポイント分子発現の検討2018

    • Author(s)
      石川雅子、中山健太郎、笹森博貴、小野瑠璃子、大西薫、山下瞳、中村康平、石橋朋佳、皆本敏子、Razia Sulutana、飯田幸司、京哲
    • Organizer
      第70回日本産科婦人科学会学術講演会
    • Related Report
      2018 Research-status Report
  • [Presentation] Lynch syndrome合併を疑う子宮峡部発生の子宮頸部明細胞癌の一例2018

    • Author(s)
      笹森博貴、中山健太郎、石橋朋佳、小野瑠璃子、佐貫薫、山下瞳、中村康平、石川雅子、皆本敏子、京哲
    • Organizer
      第70回日本産科婦人科学会学術講演会
    • Related Report
      2018 Research-status Report
  • [Presentation] 卵巣粘液性癌の発癌機構の解明~粘液性癌はType3か?~2018

    • Author(s)
      大西薫、中山健太郎、中村康平、石橋朋佳、山下瞳、小野瑠璃子、笹森博貴、Razia Sulutana、石川雅子、皆本敏子、京哲
    • Organizer
      第70回日本産科婦人科学会学術講演会
    • Related Report
      2018 Research-status Report
  • [Presentation] 本邦でのLow grade serous ovarian carcinoma(LGSOC)/serous borderline tumor(SBT)及び ovarian serous cystadenomaの遺伝子変異解析2018

    • Author(s)
      石橋朋佳、中山健太郎、笹森博貴、小野瑠璃子、山下瞳、大西薫、中村康平、石川雅子、Razia Sulutana、飯田幸司、京哲
    • Organizer
      第70回日本産科婦人科学会学術講演会
    • Related Report
      2018 Research-status Report
  • [Presentation] 脱分化型子宮体癌における免疫チェックポイント阻害剤の有効性2018

    • Author(s)
      小野瑠璃子、中山健太郎、笹森博貴、佐貫薫、山下瞳、中村康平、石橋朋佳、石川雅子、皆本敏子、京哲
    • Organizer
      第70回日本産科婦人科学会学術講演会
    • Related Report
      2018 Research-status Report
  • [Presentation] Microsatellite instability is a potential biomarker for immune checkpoint inhibitor(anti PD-1/PD-L1 antibody) in endometrial cancer2018

    • Author(s)
      Hitomi Yamashita, Kentaro Nakayama, Masako Ishikawa, Tomoka Ishibashi, Kohei Nakamura, Kaori Ohnishi, Ruriko Ono, Hiroki Sasamori, Kohji Iida, Razia Sulutana, Toshiko Minamoto, Satoru Kyo
    • Organizer
      第70回日本産科婦人科学会学術講演会
    • Related Report
      2018 Research-status Report
  • [Presentation] 網羅的がん遺伝子パネル検査によるプレシジョンメディシンの実践2018

    • Author(s)
      小野瑠璃子、中山健太郎、吉村由紀、中村康平、澤田希代加、中村秋穂、石橋朋佳、石川雅子、皆本敏子、京哲
    • Organizer
      第5回中日本産婦人科セミナー
    • Related Report
      2018 Research-status Report
  • [Presentation] 網羅的がん遺伝子パネル検査によるがんプレシジョンメディシンの実践2018

    • Author(s)
      吉村由紀、中山健太郎、中村康平、澤田希代加、中村秋穂、小野瑠璃子、石橋朋佳、石川雅子、京哲
    • Organizer
      第71回中国四国産婦人科学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Mutation analysis of Low grade serous ovarian carcinoma(LGSOC), serous borderline tumor(SBT) and ovarian serous cystadenoma in Japanese populations.2018

    • Author(s)
      Ishibashi T, Nakayama K, Yoshimura Y, Sawada K, Nakamura A, Ono R, Yamashita H, Nakamura K, Ishikawa M, Minamoto T, Kyo S
    • Organizer
      IGCS/日本婦人科腫瘍学会
    • Related Report
      2018 Research-status Report
  • [Book] Precision Medicine 2021年3月号 Personal Health Recordの利活用2021

    • Author(s)
      石橋 朋佳・中山 健太郎・京 哲
    • Total Pages
      108
    • Publisher
      北隆館
    • Related Report
      2020 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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