2019 Fiscal Year Final Research Report

Development of novel prognostic model and therapeutic strategy based on microenvironment signature in peripheral T-cell lymphoma

Research Project

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Project/Area Number	18K19565
Research Category	Grant-in-Aid for Challenging Research (Exploratory)
Allocation Type	Multi-year Fund
Review Section	Medium-sized Section 54:Internal medicine of the bio-information integration and related fields
Research Institution	Kyushu University
Principal Investigator	Akashi Koichi 九州大学, 医学研究院, 教授 (80380385)
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)
Project Period (FY)	2018-06-29 – 2020-03-31
Keywords	PTCL-NOS / 免疫微小環境 / T細胞リンパ腫 / 治療層別化
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.
Free Research Field	急性白血病や悪性リンパ腫などの造血器腫瘍の病態解明および治療開発
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。