Development of novel prognostic model and therapeutic strategy based on microenvironment signature in peripheral T-cell lymphoma
| Project/Area Number |
18K19565
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 54:Internal medicine of the bio-information integration and related fields
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| Research Institution | Kyushu University |
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Principal Investigator |
Akashi Koichi 九州大学, 医学研究院, 教授 (80380385)
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| Co-Investigator(Kenkyū-buntansha) |
宮脇 恒太 久留米大学, 医学部, 研究員 (50774709)
加藤 光次 九州大学, 大学病院, 講師 (20571764)
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| Project Period (FY) |
2018-06-29 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
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| Keywords | PTCL-NOS / 免疫微小環境 / T細胞リンパ腫 / 治療層別化 / T細胞性リンパ腫 |
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| Outline of Final Research Achievements |
Peripheral T-cell lymphoma (PTCL), not otherwise specified (NOS) is among the most common disease subtypes of PTCL, one that exhibits heterogeneous clinicopathological features. Although multiple disease-stratification models, including the cell-of-origin, have been proposed, their clinical significance remains unclear. To establish a clinically meaningful stratification model, we analyzed gene-expression signatures of tumors and tumor-infiltrating immune cells using the nCounter system. We show that gene-expression signatures representing tumor-infiltrating immune cells, but not those of cancerous T cells, dictate patient clinical outcomes. Importantly, tumor-infiltrating macrophages expressed the immune-checkpoint molecules at high levels, suggesting that checkpoint inhibitors could serve as therapeutic options for patients in this subgroup. Our study identifies clinically distinct subgroups based on microenvironment signatures and suggests a novel therapeutic strategy in PTCL-NOS.
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| Academic Significance and Societal Importance of the Research Achievements |
PTCL、特にPTCL-NOSは分類不能型と定義される通り、所謂“waste-basket disease”と位置づけられており、その治療法はおろか、病態さえも明らかになっていない。本研究は、従来の腫瘍細胞の性格よりも微小環境細胞に注目することで、明確に層別化できることを示した初めての研究である。また、既存の治療では治癒を期待できない予後不良患者に対してPD-1阻害剤が奏効する可能性を明らかにするばかりでなく、免疫チェックポイント阻害剤におけるプレシジョンメディシンの実現に資する点において、社会的意義を有する研究であると考えている。
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Report
(3 results)
Research Products
(5 results)
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[Journal Article] Aromatase is a novel neo-substrate of cereblon responsible for immunomodulatory drugs-induced thrombocytopenia. Tochigi T, Miyamoto T, Hatakeyama K, Sakoda T, Ishihara D, Irifune H, Shima T, Kato K, Maeda T, Ito T, Handa H, Akashi K, Kikushige Y.2020
Author(s)
Tochigi T, Miyamoto T, Hatakeyama K, Sakoda T, Ishihara D, Irifune H, Shima T, Kato K, Maeda T, Ito T, Handa H, Akashi K, Kikushige Y.
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Journal Title
Blood.
Volume: -
Issue: 24
Pages: 2146-2158
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A Germinal Center-Associated Microenvironmental Signature Reflects Malignant Phenotype and Outcome of Diffuse Large B-cell Lymphoma2019
Author(s)
Miyawaki K, Kato K, Sugio T, Sasaki K, Miyoshi H, Semba Y, Kikushige Y, Mori Y, Kunisaki Y, Iwasaki H, Miyamoto T, Kuo F, Aster J, Ohshima K, Maeda T, Akashi K
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Journal Title
DOI
Related Report
Open Access / Int'l Joint Research
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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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