Investigation of the effects of lenalidomide on graft-versus-host disease, with a focus on regulatory T cells.

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K17874
• 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: Kansai Medical University
• Principal Investigator: YOSHIMURA Hideaki 関西医科大学, 医学部, 助教 (70646976)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 造血幹細胞移植 / 移植片対宿主病 / レナリドミド / L-PAM

Outline of Final Research Achievements

The effect of lenalidomide on GvHD was examined in a mouse model of acute GvHD.
The initial prediction was that lenalidomide would worsen GvHD, but survival was significantly improved with lenalidomide. Regarding the histology, cellular infiltration was observed in the intestinal tract and liver, indicating that GvHD contributes to survival. No significant differences were observed in the proliferation or fractionation of T cells in spleen, especially regulatory T cells. The expression of L-PAM1 (α4β7 integrin), which is involved in T cell migration, was decreased in Foxp3-CD4+ T cells, suggesting that their migration to the intestinal tract was reduced.

Free Research Field

血液疾患

Academic Significance and Societal Importance of the Research Achievements

造血幹細胞移植は近年増加傾向である。また造血幹細胞移植後に維持療法を行うことで予後の向上を認める報告も多い。レナリドミドもまた多発性骨髄腫だけでなく悪性リンパ腫等へ適応の拡大を認めている。造血幹細胞移植前後にレナリドミドを使用する機会は増加すると予測されるが同種免疫へのレナリドミドの影響は判明しておらず、重要な合併症であるＧｖＨＤへの影響は不明確であった。
本研究においてはマウスモデルにおいてレナリドミドはGvHDを軽減することが判明し、新たな治療ターゲットの候補となりうることが示唆された。造血幹細胞の成績、ひいては血液疾患患者の予後・ＱＯＬの向上につながる可能性がある。