| Project/Area Number |
17K09963
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Kansai Medical University |
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Principal Investigator |
ITO Tomoki 関西医科大学, 医学部, 准教授 (70434826)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | IMiDs / type I IFNs / Th2 immune response / allergy / multiple myeloma / antibody drugs / dendritic cells / CCL17 / 樹状細胞 / エロツズマブ / カルフィルゾミブ / イキサゾミブ / 多発性骨髄腫 / IFN-alpha / IFN-a / Th2 / 内科 / 免疫学 |
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| Outline of Final Research Achievements |
We demonstrated that lenalidomide could sustain and potentially enhance IFN-alpha production from plasmacytoid dendritic cells (DCs). In addition, IMiDs suppressed the Th1-inducing capacity of myeloid DCs, instead promoting a Th2 response. The lenalidomide-associated rashes might be a result of an allergic response driven by Th2-axis activation. Our findings suggest clinical efficacy and rashes as a side effect of IMiDs are inextricably linked through immunostimulation. Thus, IMiDs enhances the DC-mediated IFN-alpha response and Th2 immune response, contributing to immune activation. As multiple myeloma is characterized by immune dysfunction involved in prognosis, our findings unveiled a novel target of IMiDs. IMiDs have the DC-mediated immunostimulatory activities, leading to amplification of a positive immune axis able to eliminate MM cells.
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| Academic Significance and Societal Importance of the Research Achievements |
免疫調節薬IMiDsという薬剤が、なぜ多発性骨髄腫に対し効くのか？その免疫学的解析を樹状細胞という免疫システムの司令官をターゲットとして解明し得たことが学術的意義と言える。また、この薬剤を使用した場合、有害事象の皮疹が出ると、実は潜在的に治療効果が高い可能性があることが示された。この結果は、実臨床で非常に有益な情報と考えられ社会的意義があると考える。
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