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Establishment of evaluation method of tumor immunity for application of immune checkpoint inhibitor to AML/MDS

Research Project

Project/Area Number 17K09006
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Laboratory medicine
Research InstitutionNiigata University

Principal Investigator

Shibasaki Yasuhiko  新潟大学, 医歯学総合病院, 講師 (50568540)

Co-Investigator(Kenkyū-buntansha) 成田 美和子  新潟大学, 医歯学系, 教授 (30281009)
増子 正義  新潟大学, 医歯学総合病院, 准教授 (70397115)
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: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords腫瘍免疫療法 / MLPC法 / WT1特異的細胞傷害性T細胞 / 腫瘍免疫 / MLPC / 細胞傷害性T細胞 / 免疫チェックポイント阻害薬 / WT1 / 骨髄系悪性腫瘍
Outline of Final Research Achievements

We recruited patients of myelodysplastic syndrome (MDS) and acute myeloid leukemia with myelodysplastic changes (AML-MRC) in this study. Using paired samples of bone marrow (BM) and peripheral blood (PB), we detected WT1-specific cytotoxic T cell (CTL) clones which were amplified specifically for the WT1 peptide antigen by the MLPC method, and the amount of these clones was evaluated.
Sixty-seven percent of MDS/AML-MRC patients had functional WT1-specific CTL clones in BM. The ratio of CTL clones in BM was about 10 times higher than that in PB. These results show that the site of tumor immunity targeting WT1 is mainly in BM, and there are more patients than previously suggested who might effective for tumor immunotherapy with WT1 peptide vaccines and immune checkpoint inhibitors.

Academic Significance and Societal Importance of the Research Achievements

混合リンパ球ペプチド培養法は、WT1ペプチドワクチンや免疫チェックポイント阻害薬などによる腫瘍免疫療法が有効な患者群を抽出する検査法として、有用であることを明らかにした。
WT1をターゲットとした腫瘍免疫の場は主として骨髄であり、WT1ペプチドワクチンや免疫チェックポイント阻害薬による腫瘍免疫療法が有効な症例群が、従来示唆されていた以上に存在する可能性を示した。

Report

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

    (16 results)

All 2019 2018 2017

All Journal Article (11 results) (of which Peer Reviewed: 11 results,  Open Access: 5 results) Presentation (5 results) (of which Int'l Joint Research: 4 results)

  • [Journal Article] Gemcitabine, Dexamethasone, and Cisplatin Regimen as an Effective Salvage Therapy for High-grade B-cell Lymphoma with <i>MYC</i> and <i>BCL2</i> and/or <i>BCL6</i> Rearrangements2019

    • Author(s)
      Mitobe Masaki、Kawamoto Keisuke、Suzuki Takaharu、Kiryu Maiko、Tamura Suguru、Nanba Ayako、Suwabe Tatsuya、Tanaka Tomoyuki、Fuse Kyoko、Shibasaki Yasuhiko、Masuko Masayoshi、Miyoshi Hiroaki、Ohshima Koichi、Sone Hirohito、Takizawa Jun
    • Journal Title

      Internal Medicine

      Volume: 58 Issue: 4 Pages: 575-580

    • DOI

      10.2169/internalmedicine.1686-18

    • NAID

      130007592197

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2019-02-15
    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Myeloablative and reduced-intensity conditioning in HLA-haploidentical peripheral blood stem cell transplantation using post-transplant cyclophosphamide2018

    • Author(s)
      Sugita Junichi、on behalf of the Japan Study Group for Cell Therapy and Transplantation (JSCT)、Kagaya Yusuke、Miyamoto Toshihiro、Shibasaki Yasuhiko、Nagafuji Koji、Ota Shuichi、Furukawa Tatsuo、Nara Miho、Akashi Koichi、Taniguchi Shuichi、Harada Mine、Matsuo Keitaro、Teshima Takanori
    • Journal Title

      Bone Marrow Transplantation

      Volume: 54 Issue: 3 Pages: 432-441

    • DOI

      10.1038/s41409-018-0279-1

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Heterogeneity of intrahepatic iron deposition in transfusion-dependent iron overload patients with hematological malignancies2018

    • Author(s)
      Kobayashi Hironori、Yoshimura Norihiko、Uemura Shun、Katagiri Takayuki、Tanaka Tomoyuki、Ushiki Takashi、Fuse Kyoko、Shibasaki Yasuhiko、Narita Miwako、Sone Hirohito、Masuko Masayoshi
    • Journal Title

      Leukemia Research

      Volume: 70 Pages: 41-44

    • DOI

      10.1016/j.leukres.2018.05.005

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Refinement of the Glasgow Prognostic Score as a pre-transplant risk assessment for allogeneic hematopoietic cell transplantation2018

    • Author(s)
      Shibasaki Yasuhiko、Suwabe Tatsuya、Katagiri Takayuki、Tanaka Tomoyuki、Ushiki Takashi、Fuse Kyoko、Sato Naoko、Yano Toshio、Kuroha Takashi、Hashimoto Shigeo、Narita Miwako、Furukawa Tatsuo、Sone Hirohito、Masuko Masayoshi
    • Journal Title

      International Journal of Hematology

      Volume: 108 Issue: 3 Pages: 282-289

    • DOI

      10.1007/s12185-018-2463-x

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effects of Prophylactic Foscarnet on Human Herpesvirus-6 Reactivation and Encephalitis in Cord Blood Transplant Recipients: A Prospective Multicenter Trial with an Historical Control Group2018

    • Author(s)
      Ogata Masao、Takano Kuniko、Moriuchi Yukiyoshi、Kondo Tadakazu、Ueki Toshimitsu、Nakano Nobuaki、Mori Takehiko、Uoshima Nobuhiko、Nagafuji Koji、Yamasaki Satoshi、Shibasaki Yasuhiko、Sakai Rika、Kato Koji、Choi Ilseung、Jo Yumi、Eto Tetsuya、Kako Shinichi、Oshima Kumi、Fukuda Takahiro
    • Journal Title

      Biology of Blood and Marrow Transplantation

      Volume: 印刷中 Issue: 6 Pages: 1264-1273

    • DOI

      10.1016/j.bbmt.2018.02.008

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Donor Killer Immunoglobulin-Like Receptor Haplotype B/x Induces Severe Acute Graft-versus-Host Disease in the Presence of Human Leukocyte Antigen Mismatch in T Cell-Replete Hematopoietic Cell Transplantation.2017

    • Author(s)
      Hosokai R, Masuko M, Shibasaki Y, Saitoh A, Furukawa T, Imai C.
    • Journal Title

      Biol Blood Marrow Transplant.

      Volume: 23(4) Issue: 4 Pages: 606-611

    • DOI

      10.1016/j.bbmt.2016.12.638

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Successful 5-azacytidine treatment of myeloid sarcoma and leukemia cutis associated with myelodysplastic syndrome2017

    • Author(s)
      Katagiri Takayuki、Ushiki Takashi、Masuko Masayoshi、Tanaka Tomoyuki、Miyakoshi Shukuko、Fuse Kyoko、Shibasaki Yasuhiko、Takizawa Jun、Aoki Sadao、Sone Hirohito
    • Journal Title

      Medicine

      Volume: 96 Issue: 36 Pages: e7975-e7975

    • DOI

      10.1097/md.0000000000007975

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Phase II study of intrabone single unit cord blood transplantation for hematological malignancies2017

    • Author(s)
      Murata Makoto、Maeda Yoshinobu、Masuko Masayoshi、et.al
    • Journal Title

      Cancer Science

      Volume: 108 Issue: 8 Pages: 1634-1639

    • DOI

      10.1111/cas.13291

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Glasgow Prognostic Score as a pre-transplant risk assessment for allogeneic hematopoietic cell transplantation2017

    • Author(s)
      Shibasaki Yasuhiko、Suwabe Tatsuya、Katagiri Takayuki、Tanaka Tomoyuki、Kobayashi Hironori、Fuse Kyoko、Ushiki Takashi、Sato Naoko、Yano Toshio、Kuroha Takashi、Hashimoto Shigeo、Narita Miwako、Furukawa Tatsuo、Sone Hirohito、Masuko Masayoshi
    • Journal Title

      Clinical Transplantation

      Volume: 31 Issue: 11

    • DOI

      10.1111/ctr.13103

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Successful umbilical cord blood hematopoietic stem cell transplantation in a patient with adult T-cell leukemia/lymphoma initially achieving complete remission with anti-CC chemokine receptor 4 antibody combined chemotherapy2017

    • Author(s)
      Suwabe T, Shibasaki Y, Kaihatsu A, Katagiri T, Miyakoshi S, Fuse K, Kobayashi H, Ushiki T, Moriyama M, Takizawa J, Narita M, Sone H, Masuko M.
    • Journal Title

      Rinsho Ketsueki

      Volume: 58 Issue: 1 Pages: 32-36

    • DOI

      10.11406/rinketsu.58.32

    • NAID

      130005394599

    • ISSN
      0485-1439, 1882-0824
    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Peripheral T-cell lymphoma, not otherwise specified: a retrospective single-center analysis2017

    • Author(s)
      鈴木 隆晴、柴崎 康彦、森山 雅人、増子 正義、成田 美和子、曽根 博仁、青木 定夫、中村 直哉、大島 孝一、瀧澤 淳、河本 啓介、田村 秀、上村 駿、海發 茜、根本 洋樹、小林 弘典、牛木 隆志、布施 香子
    • Journal Title

      Rinsho Ketsueki

      Volume: 58 Issue: 8 Pages: 905-911

    • DOI

      10.11406/rinketsu.58.905

    • NAID

      130006067957

    • ISSN
      0485-1439, 1882-0824
    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] Monitoring of Persistent CTLs over 10 Years Using MLPC after WT1 Peptide Vaccine in a CML Patient.2019

    • Author(s)
      Suwabe T, Ogawa S, Goto W, Sato H, Fuse K, Shibasaki Y, Sone H, Masuko M, Narita M.
    • Organizer
      The 10th JSH International Symposium 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] MLPC法はMDS患者の末梢血および骨髄血に存在するWT1特異的CD8陽性T細胞の検出に有用である2019

    • Author(s)
      諏訪部達也、柴崎康彦、佐藤廣幸、田村秀、片桐隆幸、布施香子、曽根博仁、成田美和子、増子正義.
    • Organizer
      日本血液学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Prediction of Acute Graft-Versus-Host Disease Following Allogeneic Hematopoietic Stem Cell Transplantation Using a Machine Learning Algorithm2018

    • Author(s)
      Arai Y, Kondo T, Fuse K, Shibasaki Y, Masuko M, Sugita J, Teshima T, Uchida N, Fukuda T, Ohashi K, Ozawa Y, Ichinohe T, Kanda Y, Atsuta Y
    • Organizer
      2018 ASH Annual Meeting & Expo
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Distinct Effects of Chondroitin Sulfate on Hematopoietic Cells and the Stromal Microenvironment in Bone Marrow Hematopoiesis2018

    • Author(s)
      Katagiri, T; Ushiki, T; Kawasaki, A; Uemura, S; Suwabe, T; Tanaka, T; Fuse, K; Shibasaki, Y; Sone, H; Igarashi, M; Masuko, M
    • Organizer
      2018 ASH Annual Meeting & Expo
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Further Prognostic Factors for Stratification of Patients in the High-Risk HCT-CI Group Undergoing Allogeneic HCT2017

    • Author(s)
      Yasuhiko Shibasaki, Tatsuya Suwabe, Takayuki Katagiri, Tomoyuki Tanaka, Hironori Kobayashi, Kyoko Fuse, Takashi Ushiki, Miwako Narita, Hirohito Sone, Masayoshi Masuko
    • Organizer
      第59回アメリカ血液学会 (59th ASH Annual Meeting)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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

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