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

• Project/Area Number: 17K09006
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Niigata 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: ¥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。

Research Products

• [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> Rearrangements (2019)
  • 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
  • Peer Reviewed
• [Journal Article] Myeloablative and reduced-intensity conditioning in HLA-haploidentical peripheral blood stem cell transplantation using post-transplant cyclophosphamide (2018)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Heterogeneity of intrahepatic iron deposition in transfusion-dependent iron overload patients with hematological malignancies (2018)
  • 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
  • Peer Reviewed
• [Journal Article] Refinement of the Glasgow Prognostic Score as a pre-transplant risk assessment for allogeneic hematopoietic cell transplantation (2018)
  • 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
  • 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 Group (2018)
  • 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
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Successful 5-azacytidine treatment of myeloid sarcoma and leukemia cutis associated with myelodysplastic syndrome (2017)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Phase II study of intrabone single unit cord blood transplantation for hematological malignancies (2017)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] The Glasgow Prognostic Score as a pre-transplant risk assessment for allogeneic hematopoietic cell transplantation (2017)
  • 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
  • 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 chemotherapy (2017)
  • 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
  • Peer Reviewed
• [Journal Article] Peripheral T-cell lymphoma, not otherwise specified: a retrospective single-center analysis (2017)
  • 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
  • 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
  • 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
• [Presentation] Prediction of Acute Graft-Versus-Host Disease Following Allogeneic Hematopoietic Stem Cell Transplantation Using a Machine Learning Algorithm (2018)
  • 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
  • Int'l Joint Research
• [Presentation] Distinct Effects of Chondroitin Sulfate on Hematopoietic Cells and the Stromal Microenvironment in Bone Marrow Hematopoiesis (2018)
  • 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
  • Int'l Joint Research
• [Presentation] Further Prognostic Factors for Stratification of Patients in the High-Risk HCT-CI Group Undergoing Allogeneic HCT (2017)
  • 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)
  • Int'l Joint Research