Characterization molecular and immunologic features of CML stem cells for treatment-free remission.

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08375
• 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: Kindai University
• Principal Investigator: MATSUMUTA Itaru 近畿大学, 医学部, 教授 (00294083)
• Co-Investigator(Kenkyū-buntansha): 田中 宏和 近畿大学, 医学部, 准教授 (40360846) ; 頼 晋也 近畿大学, 医学部, 講師 (70460855) ; 森田 泰慶 近畿大学, 医学部, 講師 (80411594)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 慢性骨髄性白血病 / 分子標的 / 腫瘍免疫

Outline of Final Research Achievements

In this study, we analyzed immune evasion mechanisms of residual chronic myeloid leukemia stem cells　(CML-LSCs) during the treatment with tyrosine kinase inhibitors (TKIs). Both expression of immune checkpoint molecule, PDL1 and activation of immunosuppressive enzyme, IDO1 were induced through the activation of CD120a/NF-κB signaling pathway in phenotypically defined CD34+38-120a+225+ cells, which we previously identified as CML-LSC. Furthermore, CML-LSCs suppressed cytotoxic T cell activity and induced a local recruitment of immunosuppressive populations such as regulatory T cells and myeloid-derived suppressor cells, leading to an immunosuppressive bone marrow milieu undergoing TKI therapy.

Free Research Field

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Academic Significance and Societal Importance of the Research Achievements

本研究は、CMLの免疫回避機構における腫瘍免疫とアミノ酸代謝との関連を明らかにしたものであり学術的意義は高い。本研究により、組織内IDO1活性を指標としたTKI の中止可能な症例の選別法だけでなく、治癒に向けたIDO1阻害によるCML-LSCに対する新規治療法を開発する上で、重要な知見が得られたと考えられる。