The lymphoma microenvironment is a novel therapeutic target in the treatment of patients with B-cell lymphoma
| Project/Area Number |
16K09875
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Kyushu University |
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Principal Investigator |
Kato Koji 九州大学, 大学病院, 講師 (20571764)
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| Research Collaborator |
Miyawaki Kohta
Sugio Takeshi
Sasaki Kensuke
Ohshima Koichi
Akashi Koichi
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 悪性リンパ腫 / 微小環境 |
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| Outline of Final Research Achievements |
Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell malignancy with varying prognosis. We assess the clinical impact of the tumor microenvironment on the clinical outcomes and pathophysiological, molecular signatures in DLBCL using transcriptome analysis by nCounter and DNA sequencing. The present study showed that the presence of normal germinal center (GC)-microenvironmental cells, including follicular T, macrophage/dendritic, and stromal cells, in lymphoma tissue is highly associated with better prognosis. Novel prognostic model, based on quantitation of ICOS, CD11c, and FGFR1 transcripts as distinct GC-microenvironmental cell markers, clearly identified patients with graded prognosis. We also found an increased incidence of unfavorable molecular signatures such as poor prognostic genomic alterations or proliferation-related gene expression in DLBCL tissues lacking GC-microenvironmental cells. The specific microenvironmental signature in DLBCL predicts clinical outcomes.
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| Academic Significance and Societal Importance of the Research Achievements |
従来までのDLBCL予後層別化は、B細胞リンパ腫自体の遺伝子プロファイリングが中心で、微小環境との関連について、ほとんど研究されてこなかった。本研究により、リンパ腫微小環境のパターンが、DLBCLの予後をより精確に層別化しうることが分かった。治療開発という側面においても、本研究は、従来行われてきた腫瘍細胞（B細胞）そのものを標的とする治療を革新する次世代の新規治療法の創出に役立つことが期待されうる。
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Report
(4 results)
Research Products
(37 results)
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[Journal Article] Microenvironmental immune cell signatures dictate clinical outcomes for PTCL-NOS.2018
Author(s)
Sugio T, Miyawaki K, Kato K, Sasaki K, Yamada K, Iqbal J, Miyamoto T, Ohshima K, Maeda T, Miyoshi H, Akashi K.
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Journal Title
Blood Advances
Volume: 2
Issue: 17
Pages: 2242-2252
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] A distinct subtype of Epstein Barr virus positive T/NK-cell lymphoproliferative disorder: Adult patients with chronic active Epstein Barr virus infection-like features.2017
Author(s)
Kawamoto K, Miyoshi H, Suzuki T, Kozai Y, Kato K, Miyahara M, Yujiri T, Choi I, Fujimaki K, Muta T, Kume M, Moriguchi S, Tamura S, Kato T, Tagawa H, Makiyama J, Kanisawa Y, Sasaki Y, Kurita D, Yamada K, Shimono J, Sone H, Takizawa J, Seto M, Kimura H, Ohshima K.
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Journal Title
Haematologica.
Volume: Epub
Issue: 6
Pages: 1018-1028
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Mogamulizumab Treatment Prior to Allogeneic Hematopoietic Stem Cell Transplantation Induces Severe Acute Graft-versus-Host Disease.2016
Author(s)
Sugio T, Kato K, Aoki T, Ohta T, Saito N, Yoshida S, Kawano I, Henzan H, Kadowaki M, Takase K, Muta T, Miyawaki K, Yamauchi T, Shima T, Takashima S, Mori Y, Yoshimoto G, Kamezaki K, Takenaka K, Iwasaki H, Ogawa R, Ohno Y, Eto T, Kamimura T, Miyamoto T, Akashi K.
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Journal Title
Biol Blood Marrow Transplant.
Volume: 22
Issue: 9
Pages: 1608-1614
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] PD-L1 expression on neoplastic or stromal cell is respectively poor or good prognostic factor for adult T-cell leukemia/lymphoma.2016
Author(s)
Miyoshi H, Kiyasu J, Kato T, Yoshida N, Shimono J, Yokoyama S, Taniguchi H, Sasaki Y, Kurita D, Kawamoto K, Kato K, Imaizumi Y, Seto M, Ohshima K.
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Journal Title
Blood.
Volume: 128
Issue: 10
Pages: 1374-1381
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Pretransplantation Anti-CCR4 Antibody Mogamulizumab Against Adult T-Cell Leukemia/Lymphoma Is Associated With Significantly Increased Risks of Severe and Corticosteroid-Refractory Graft-Versus-Host Disease, Nonrelapse Mortality, and Overall Mortality.2016
Author(s)
Fuji S, Inoue Y, Utsunomiya A, Moriuchi Y, Uchimaru K, Choi I, Otsuka E, Henzan H, Kato K, Tomoyose T, Yamamoto H, Kurosawa S, Matsuoka K, Yamaguchi T, Fukuda T.
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Journal Title
J Clin Oncol
Volume: 34(28)
Issue: 28
Pages: 3426-33
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Enhanced Reconstitution of Human Erythropoiesis and Thrombopoiesis in an Immunodeficient Mouse Model with Kit(Wv) Mutations.2016
Author(s)
A. Yurino, K. Takenaka, T. Yamauchi, T. Nunomura, Y. Uehara, F. Jinnouchi, K. Miyawaki, Y. Kikushige, K. Kato, T. Miyamoto, H. Iwasaki, Y. Kunisaki, *K. Akashi
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Journal Title
Stem Cell Reports
Volume: 7
Issue: 3
Pages: 425-438
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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