Genomic instability and tumorigenesis by CD30 in HTLV-1-infected cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07379
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Kitasato University
• Principal Investigator: Horie Ryouichi 北里大学, 医療衛生学部, 教授 (80229228)
• Co-Investigator(Kenkyū-buntansha): 渡邉 真理子 北里大学, 医療衛生学部, 助教 (90270701)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: CD30 / HTLV-1 / ATL / genomic instability / ROS / PI3K / PD-L1 / Tax

Outline of Final Research Achievements

CD30 stimulation in HTLV-1-infected cells induced DNA damages, which triggered chromatin bridges and cytokinesis failure, resulting in the accumulation of genomic abnormalities. DNA damages by CD30 stimulation were caused by generation of reactive oxygen species (ROS) through activation of phosphatidylinositol-3 kinase (PI3K). CD30 stimulation also induced PD-L1(CD274), which might attenuate exclusion of the HTLV-1-infected cells by immune cells from the body. Tax did not induce CD30 and these 2 molecules appeared to independently involve induction of genomic instability and progression of disease statuses.

Free Research Field

人体病理学

Academic Significance and Societal Importance of the Research Achievements

本研究によりCD30はゲノム異常の蓄積、遺伝子発現の変化、PD-L1の誘導によりHTLV-1感染細胞のクローン進化や免疫回避に関与してHTLV-1感染者の病態の進展に関与しうることが示唆された。CD30を分子標的とした新規治療法がATLの発症予防と治療に重要な役割を果たしうること、PD-L1誘導に関与しているNF-κBの阻害薬開発の重要性を示唆した。