Elucidation of immunostimulatory mechanism of IMiDs and antibody-drugs for optimized myeloma treatment

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09963
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Kansai Medical University
• Principal Investigator: ITO Tomoki 関西医科大学, 医学部, 准教授 (70434826)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: IMiDs / type I IFNs / Th2 immune response / allergy / multiple myeloma / antibody drugs / dendritic cells / CCL17

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.

Free Research Field

血液免疫学　樹状細胞　造血器腫瘍学

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。