Frequency analysis of graft-versus-host reactive T cell clones in human acute graft-versus-host disease tissues

• Project/Area Number: 18K08321
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Nagoya University
• Principal Investigator: MURATA Makoto 名古屋大学, 医学系研究科, 准教授 (40378063)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 造血幹細胞移植 / 移植片対宿主病 / T細胞 / T細胞受容体 / アロ抗原

Outline of Final Research Achievements

The T cell repertoire in the skin tissues with acute graft-versus-host disease (GVHD) was more skewed when acute GVHD was severe or refractory. The frequent T cell clones in the GVHD skin tissues with a treatment failure were different from those in the GVHD skin tissues at diagnosis. Mixed culture of peripheral blood mononuclear cells that were obtained from pre-transplant recipient and donor could not identify the GVHD-associated T cell clones in the GVHD skin tissues.

Academic Significance and Societal Importance of the Research Achievements

本研究成果はヒトの急性GVHDの病態解明に寄与するとともに、急性GVHDに対する新しい予防戦略、治療戦略の開発基盤になるものと期待される。例えば、生検皮膚組織を用いて急性GVHDの病理診断を行う際、T細胞浸潤や組織破壊の程度に加えて、TCRレパトアの偏りの強さも調べることで、GVHDの重症度をより正確に判定したり、その後の治療反応性を予測したりすることができる可能性がある。このような研究成果は、移植成績の向上、難治性血液疾患患者の予後改善につながるものと期待される。

Research Products

• [Journal Article] A multicenter phase II study of intrabone single-unit cord blood transplantation without antithymocyte globulin. (2021)
  • Author(s): Nishida T, Kobayashi T, Sawa M, Masuda S, Shibasaki Y, Goto T, Fukuhara N, Fujii N, Ikegame K, Sugita J, Ikeda T, Kuwatsuka Y, Suzuki R, Najima Y, Doki N, Kato T, Inagaki Y, Utsu Y, Aotsuka N, Masuko M, Terakura S, Onishi Y, Maeda Y, Okada M, Teshima T, Murata M.
  • Journal Title: Annals of Hematology Volume: 100 Issue: 3 Pages: 743-752
  • DOI: 10.1007/s00277-020-04365-z
  • NAID: 120007147363
  • Peer Reviewed
• [Journal Article] Allogeneic Hematopoietic Stem Cell Transplantation for Post-essential Thrombocythemia and Post-polycythemia Vera Myelofibrosis (2020)
  • Author(s): Murata M, Suzuki R, Nishida T, Shirane S, Shimazu Y, Minami Y, Mori T, Doki N, Kanda Y, Uchida N, Tanaka M, Ishikawa J, Togitani K, Fukuda T, Ichinohe T, Atsuta Y, Nagamura-Inoue T, Kiyoi H.
  • Journal Title: Internal Medicine Volume: 59 Issue: 16 Pages: 1947-1956
  • DOI: 10.2169/internalmedicine.4375-19
  • NAID: 130007887720
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2020-08-15
  • Peer Reviewed / Open Access
• [Journal Article] Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Myelodysplastic/Myeloproliferative Neoplasms-Unclassifiable: A Retrospective Nationwide Study of the Japan Society for Hematopoietic Cell Transplantation. (2020)
  • Author(s): Kurosawa S, Shimomura Y, Tachibana T, Ishiyama K, Ota S, Kobayashi T, Uchida N, Fukushima K, Ashida T, Matsuoka K, Kanda J, Ichinohe T, Atsuta Y, Murata M, Aoki J.
  • Journal Title: Biology of Blood and Marrow Transplantation Volume: 26 Issue: 9 Pages: 1607-1611
  • DOI: 10.1016/j.bbmt.2020.05.013
  • Peer Reviewed
• [Journal Article] Capturing Differential Allele-Level Expression and Genotypes of All Classical HLA Loci and Haplotypes by a New Capture RNA-Seq Method. (2020)
  • Author(s): Yamamoto F, Suzuki S, Mizutani A, Shigenari A, Ito S, Kametani Y, Kato S, Fernandez-Vina M, Murata M, Morishima S, Morishima Y, Tanaka M, Kulski JK, Bahram S, Shiina T.
  • Journal Title: Front Immunol. Volume: 11 Pages: 941-941
  • DOI: 10.3389/fimmu.2020.00941
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Prospective evaluation of alternative donor from unrelated donor and cord blood in adult acute leukemia and myelodysplastic syndrome (2020)
  • Author(s): Terakura S, Nishida T, Sawa M, Kato T, Miyao K, Ozawa Y, Goto T, Kohno A, Ozeki K, Onishi Y, Fukuhara N, Fujii N, Yokoyama H, Kasai M, Iida H, Kanemura N, Endo T, Ago H, Onizuka M, Iyama S, Nawa Y, Nakamae M, Nagata Y, Kurahashi S, Tomiya Y, Yanagisawa A, Suzuki R, Kuwatsuka Y, Atsuta Y, Miyamura K, Murata M
  • Journal Title: Bone Marrow Transplantation Volume: -- Issue: 7 Pages: 1399-1409
  • DOI: 10.1038/s41409-020-0859-8
  • NAID: 120006891238
  • Peer Reviewed
• [Journal Article] Donor single nucleotide polymorphism in ACAT1 affects the incidence of graft-versus-host disease after bone marrow transplantation. (2020)
  • Author(s): Kamoshita S, Murata M, Koyama D, Julamanee J, Okuno S, Takagi E, Miyao K, Goto T, Ozawa Y, Miyamura K, Terakura S, Nishida T, Kiyoi H.
  • Journal Title: International Journal of Hematology Volume: 111 Issue: 1 Pages: 112-119
  • DOI: 10.1007/s12185-019-02739-2
  • NAID: 120006848998
  • Peer Reviewed
• [Journal Article] Impact of homozygous conserved extended HLA haplotype on single cord blood transplantation: Lessons for induced pluripotent stem cell banking and transplantation in allogeneic settings. (2020)
  • Author(s): Morishima Y, Morishima S, Murata M, Arima N, Uchida N, Sugio Y, Takahashi S, Matsuhashi Y, Onizuka M, Eto T, Nagafuji K, Onishi Y, Inoue M, Atsuta Y, Fukuda T, Ichinohe T, Kato S, Kanda J.
  • Journal Title: Biology of Blood and Marrow Transplantation Volume: 26 Issue: 1 Pages: 132-138
  • DOI: 10.1016/j.bbmt.2019.09.009
  • Peer Reviewed
• [Journal Article] Prospective Phase 2 Study of Umbilical Cord Blood Transplantation in Adult Acute Leukemia and Myelodysplastic Syndrome (2020)
  • Author(s): Terakura S, Nishida T, Sawa M, Kato T, Miyao K, Ozawa Y, Kohno A, Onishi Y, Fukuhara N, Kasai M, Fujii N, Yokoyama H, Iida H, Kanemura N, Fujieda A, Ago H, Tsutsumi Y, Nakamura F, Yago K, Moriuchi Y, Ota S, Ohashi H, Yanagisawa A, Suzuki R, Kuwatsuka Y, Atsuta Y, Miyamura K, Murata M
  • Journal Title: Biology of Blood and Marrow Transplantation Volume: 26 Issue: 1 Pages: 139-144
  • DOI: 10.1016/j.bbmt.2019.09.021
  • Peer Reviewed
• [Journal Article] Analysis of glutathione S-transferase and cytochrome P450 gene polymorphism in recipients of dose-adjusted busulfan-cyclophosphamide conditioning (2020)
  • Author(s): Terakura S, Onizuka M, Fukumoto M, Kuwatsuka Y, Kohno A, Ozawa Y, Miyamura K, Inagaki Y, Sawa M, Atsuta Y, Suzuki R, Naoe T, Morishita Y, Murata M
  • Journal Title: Int J Hematol Volume: 111 Issue: 1 Pages: 84-92
  • DOI: 10.1007/s12185-019-02741-8
  • Peer Reviewed
• [Journal Article] Comparison of outcomes of allogeneic transplantation for primary myelofibrosis among hematopoietic stem cell source groups. (2019)
  • Author(s): Murata M, Takenaka K, Uchida N, Ozawa Y, Ohashi K, Kim SW, Ikegame K, Kanda Y, Kobayashi H, Ishikawa J, Ago H, Hirokawa M, Fukuda T, Atsuta Y, Kondo T.
  • Journal Title: Biology of Blood and Marrow Transplantation Volume: 25 Issue: 8 Pages: 1536-1543
  • DOI: 10.1016/j.bbmt.2019.02.019
  • Peer Reviewed
• [Journal Article] Quantitative Assessment of T Cell Clonotypes in Human Acute Graft-versus-Host Disease Tissues. (2019)
  • Author(s): Koyama D, Murata M, Hanajiri R, Akashi T, Okuno S, Kamoshita S, Julamanee J, Takagi E, Miyao K, Sakemura R, Goto T, Terakura S, Nishida T, Kiyoi H
  • Journal Title: Biol Blood Marrow Transplant Volume: 25 Issue: 3 Pages: 417-423
  • DOI: 10.1016/j.bbmt.2018.10.012
  • Peer Reviewed / Open Access
• [Journal Article] Impacts of thymoglobulin in patients with acute leukemia in remission undergoing allogeneic HSCT from different donors. (2019)
  • Author(s): Wakamatsu M, Terakura S, Ohashi K, Fukuda T, Ozawa Y, Kanamori H, Sawa M, Uchida N, Ota S, Matsushita A, Kanda Y, Nakamae H, Ichinohe T, Kato K, Murata M, Atsuta Y, Teshima T.
  • Journal Title: Blood Adv Volume: 3 Issue: 2 Pages: 105-115
  • DOI: 10.1182/bloodadvances.2018025643
  • Peer Reviewed / Open Access
• [Journal Article] Clinical implications of t(11;14) in patients with multiple myeloma undergoing autologous stem cell transplantation. (2019)
  • Author(s): Takamatsu H, Yamashita T, Kurahashi S, Saitoh T, Kondo T, Maeda T, Nakazawa H, Murata M, Narita T, Kuroda J, Hashimoto H, Kawamura K, Miyamoto T, Honda S, Ichinohe T, Atsuta Y, Sunami K.
  • Journal Title: Biol Blood Marrow Transplant Volume: 25 Issue: 3 Pages: 474-479
  • DOI: 10.1016/j.bbmt.2018.11.003
  • Peer Reviewed
• [Journal Article] Impact of graft-versus-host disease on relapse and survival after allogeneic stem cell transplantation for pediatric leukemia. Bone Marrow Transplant. (2019)
  • Author(s): Kato M, Kurata M, Kanda J, Kato K, Tomizawa D, Kudo K, Yoshida N, Watanabe K, Shimada H, Inagaki J, Koh K, Goto H, Kato K, Cho Y, Yuza Y, Ogawa A, Okada K, Inoue M, Hashii Y, Teshima T, Murata M, Atsuta Y.
  • Journal Title: Bone Marrow Transplant Volume: 54 Issue: 1 Pages: 68-75
  • DOI: 10.1038/s41409-018-0221-6
  • Peer Reviewed
• [Journal Article] Introduction of genetically modified CD3ζ improves proliferation and persistence of antigen-specific CTLs. (2018)
  • Author(s): Miyao K, Terakura S, Okuno S, Julamanee J, Watanabe K, Hamana H, Kishi H, Sakemura R, Koyama D, Goto T, Nishida T, Murata M, Kiyoi H.
  • Journal Title: Cancer Immunol Res Volume: 6 Issue: 6 Pages: 733-744
  • DOI: 10.1158/2326-6066.cir-17-0538
  • Peer Reviewed
• [Presentation] HSCT for Myelofibrosis in Japan. (2020)
  • Author(s): Murata M.
  • Organizer: The International Congress of BMT 2020
  • Int'l Joint Research / Invited
• [Presentation] Phase I study of cord blood transplantation with intra-bone marrow injection of MSC. (2020)
  • Author(s): Goto T, Murata M, Nishida T, Terakura S, Kamoshita S, Ishikawa Y, Ushijima Y, Adachi Y, Kato K, Hirakawa A, Nishiwaki S, Nishio N, Takahashi Y, Kodera Y, Matsushita T, Kiyoi H.
  • Organizer: 第82回日本血液学会学術集会
• [Presentation] Prospective evaluation of alternative donor from unrelated donor and cord blood in adult AL and MDS. (2020)
  • Author(s): Goto T, Terakura S, Nishida T, Sawa M, Kato T, Miyao K, Ozawa Y, Kohno A, Ozeki K, Onishi Y, Fukuhara N, Fujii N, Yokoyama H, Kasai M, Iida H, Kanemura N, Endo T, Ago H, Onizuka M, Iyama S, Nagata Y, Kurahashi S, Yanagisawa A, Suzuki R, Kuwatsuka Y, Atsuta Y, Miyamura K, Murata M.
  • Organizer: 第82回日本血液学会学術集会
• [Presentation] ヒト急性GVHDにおけるT細胞応答、診断、治療. (2019)
  • Author(s): 村田 誠.
  • Organizer: 第67回日本輸血・細胞治療学会
• [Presentation] ヒト急性移植片対宿主病組織内高頻度T細胞クローンの経時的変化. (2019)
  • Author(s): 岡崎翔一郎, 村田 誠, 小山大輔, 堺 寿保, 牛島洋子, 鴨下園子, 奥野真吾, 高木えり奈, Jakrawadee Julamanee, 渡邊慶介, 今橋伸彦, 寺倉精太郎, 西田徹也, 清井 仁.
  • Organizer: 第28回日本組織適合性学会大会
• [Presentation] 原発性骨髄線維症に対する同種造血幹細胞移植の成績：移植ソース間の比較. (2019)
  • Author(s): 村田 誠, 竹中克斗, 内田直之, 小澤幸泰, 大橋一輝, 金 成元, 池亀和博, 廣川 誠, 福田隆浩, 熱田由子, 近藤 健.
  • Organizer: 第81回日本血液学会学術集会
• [Presentation] Phase I Study of Cord Blood Transplantation with Intra-Bone Marrow Injection of Mesenchymal Stem Cells. (2019)
  • Author(s): Goto T, Murata M, Nishida T, Terakura S, Kamoshita S, Ishikawa Y, Ushijima Y, Adachi Y, Kato K, Hirakawa A, Nishiwaki S, Nishio N, Takahashi Y, Kodera Y, Matsushita T, Kiyoi H.
  • Organizer: The 61th Annual Meeting of the American Society of Hematology
  • Int'l Joint Research
• [Presentation] Prospective Evaluation of Alternative Donor from Unrelated Volunteer Donor and Cord Blood in Adult Acute Leukemia and Myelodysplastic Syndrome: No Difference between Unrelated Donor and Cord Blood. (2019)
  • Author(s): Terakura S, Nishida T, Sawa M, Kato T, Miyao K, Ozawa Y, Goto T, Kohno A, Ozeki K, Onishi Y, Fukuhara N, Fujii N, Yokoyama H, Kasai M, Iida H, Kanemura N, Endo T, Ago H, Onizuka M, Iyama S, Nawa Y, Nakamae M, Nagata Y, Kurahashi S, Tomiya Y, Yanagisawa A, Suzuki R, Kuwatsuka Y, Atsuta Y, Miyamura K, Murata M.
  • Organizer: The 61th Annual Meeting of the American Society of Hematology
  • Int'l Joint Research
• [Presentation] 造血幹細胞移植における間葉系幹細胞の臨床応用. (2019)
  • Author(s): 村田 誠.
  • Organizer: 第18回日本再生医療学会総会
  • Invited
• [Presentation] 間葉系幹細胞と造血幹細胞移植. (2019)
  • Author(s): 村田 誠.
  • Organizer: 第41回日本造血細胞移植学会総会
  • Invited
• [Presentation] 本態性血小板血症および真性赤血球増加症から移行した二次性骨髄線維症に対する同種移植の成績. (2019)
  • Author(s): 村田 誠、鈴木律朗、西田徹也、森 毅彦、福田隆浩、一戸辰夫、熱田由子、清井 仁.
  • Organizer: 第41回日本造血細胞移植学会総会
• [Presentation] The association between a SNP in the SOAT1 gene and the incidence of chronic GVHD after allo-HSCT. (2018)
  • Author(s): Kamoshita S, Murata M, Koyama D, Sakai T, Okazaki S, Okuno S, Julamanee J, Takagi E, Miyao K, Goto T, Ozawa Y, Miyamura K, Terakura S, Nishida T, Kiyoi H.
  • Organizer: 第80回日本血液学会学術集会
• [Presentation] Comparison of outcomes of allogeneic hematopoietic cell transplantation for primary myelofibrosis among stem cell source groups. (2018)
  • Author(s): Murata M, Takenaka K, Uchida N, Ozawa Y, Ohashi K, Kim SW, Ikegame K, Atsuta Y, Hirokawa M, Fukuda T, Kondo T.
  • Organizer: The 60th annual meeting of the American Society of Hematology
  • Int'l Joint Research