Research Project
Grant-in-Aid for Scientific Research (C)
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.
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。
All 2021 2020 2019 2018 2017
All Journal Article (27 results) (of which Peer Reviewed: 27 results, Open Access: 24 results) Presentation (14 results) (of which Int'l Joint Research: 4 results)
Int J Hematol.
Volume: 113 Issue: 3 Pages: 395-403
10.1007/s12185-020-03032-3
Internal Medicine
Volume: 59 Issue: 21 Pages: 2745-2749
10.2169/internalmedicine.4871-20
130007934222
Cancers (Basel)
Volume: 12(6) Issue: 6 Pages: 1444-1444
10.3390/cancers12061444
Volume: 111 Issue: 6 Pages: 912-825
10.1007/s12185-020-02843-8
Cancer Science
Volume: 111 Issue: 10 Pages: 3714-3725
10.1111/cas.14580
International Journal of Hematology
Volume: Epub ahead of print Issue: 1 Pages: 24-32
10.1007/s12185-020-02878-x
120007036312
Nature Communications
Volume: 11 Issue: 1 Pages: 4147-4147
10.1038/s41467-020-17666-8
Leukemia
Volume: 33 Issue: 2 Pages: 358-370
10.1038/s41375-018-0233-7
British Journal of Haematology
Volume: 184 Issue: 2 Pages: 121-121
10.1111/bjh.15689
Frontiers in Immunology
Volume: 9
10.3389/fimmu.2018.03031
Cells
Volume: 8 Issue: 3 Pages: 226-226
10.3390/cells8030226
Leukemia & Lymphoma
Volume: 60 Issue: 2 Pages: 1-3
10.1080/10428194.2019.1665665
Int J Hematol
Volume: 109 Issue: 4 Pages: 426-439
10.1007/s12185-019-02613-1
Volume: 110 Issue: 6 Pages: 675-682
10.1007/s12185-019-02736-5
Cancers (Basel).
Volume: 10 Issue: 9 Pages: 304-304
10.3390/cancers10090304
120007133039
Leukemia Research Reports
Volume: 10 Pages: 7-10
10.1016/j.lrr.2018.07.001
Volume: 109 Issue: 10 Pages: 3209-3215
10.1111/cas.13739
Volume: 10 Pages: 1-3
10.1016/j.lrr.2018.06.001
Frontiers in Oncology
Volume: 8 Pages: 204-204
10.3389/fonc.2018.00204
Support Care Cancer
Volume: 26 Issue: 12 Pages: 4187-4198
10.1007/s00520-018-4292-0
Annals of Hematology
Volume: 97 Issue: 6 Pages: 1095-1096
10.1007/s00277-018-3272-2
Rinsho Ketsueki
Volume: 59 Issue: 1 Pages: 13-26
10.11406/rinketsu.59.13
130006337957
Volume: 107 Issue: 5 Pages: 541-550
10.1007/s12185-018-2416-4
Volume: 107 Issue: 5 Pages: 535-540
10.1007/s12185-018-2401-y
Leukemia Research
Volume: 66 Pages: 20-27
10.1016/j.leukres.2018.01.008
120006473597
Volume: 107 Issue: 3 Pages: 327-336
10.1007/s12185-017-2353-7
Volume: 107 Issue: 2 Pages: 185-193
10.1007/s12185-017-2334-x