Development of clinical method for chronic GVHD focused on organ fibrosis

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17399
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Mie University
• Principal Investigator: Ino Kazuko 三重大学, 医学系研究科, 助教 (60775568)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 同種造血幹細胞移植 / 慢性GVHD / 臓器・組織線維化 / 免疫関連分子

Outline of Final Research Achievements

Hematopoietic stem cell transplantation (HSCT) has become the curable treatment for the patient of hematological malignancy. Graft vs host disease (GVHD) is the most important problem. In this study, we focused on the fibrocyte and analyzed the pathophysiology of chronic GVHD. Additionally, we assess the association of immunosuppressive agents with outcome. In the study of mice model, activated monocytes were appeared to peripheral blood after 2 weeks. In the study of human, activated monocytes were appeared peripheral blood about day 30 and these cells were detectable for long time. In the study of immunosuppressive agents, at the time of day 90, these agents and relapse had been related to significant difference. These data suggest that activated monocytes were appeared in early stage after HSCT and interact to immunological cells. And immunosuppressive status leaded to relapse after HSCT. Further experiments are needed for more detail analysis.

Free Research Field

造血幹細胞移植

Academic Significance and Societal Importance of the Research Achievements

本研究は同種移植後の慢性GVHDについて、繊維芽細胞に着目した上で、慢性GVHDマウスモデルを用いた検討、ヒト臨床検体を用いた検討を行い、その病態解明を行っている。また、ヒト臨床検体を用いて、同種移植後の免疫関連分子と移植後の免疫病態、GVHD、GVL効果についても検討を行っている。この結果、慢性GVHDにおける活性化単球の長期に渡る免疫病態への影響が示唆され、また、同種移植後の免疫抑制状態が原疾患の再発に繋がることが示唆された。これら結果は、同種移植後の病態解明に繋がると伴に、同種移植後治療成績の向上に結び付くことが期待できる。