ADAM10 related tumor microenvironment in Hodgkin lymphoma

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K16566
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Saitama Medical University
• Principal Investigator: Wataru Masuda 埼玉医科大学, 医学部, 助教 (00623464)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: Hodgkinリンパ腫 / 癌微小環境 / ADAM10

Outline of Final Research Achievements

The aim of the study is to clarify the function of a disintegrin and metalloproteinases 10 (ADAM10) on tumor microenvironment in Hodgkin lymphoma. We found that Hodgkin lymphoma cell line L-428 caused homotypic cell aggregation due to ADAM10 selective inhibitor (GI254023X). We extracted RNA from both L-428 cell line with or without the inhibitor and RNA microarray analysis revealed the alteration in gene expression related to ADAM10. We focused on cytokines and immune markers among these genes and analyzed immunohistochemical study using patient tumor tissue. We found that two types of favorable prognosis marker; loss of CXCR5 on Hodgkin/Reed-Sternberg (HRS) cells and expression of MHC class Ⅱ on non-tumor cells around HRS cells.

Free Research Field

病理学

Academic Significance and Societal Importance of the Research Achievements

a disintegrin and metalloproteinases 10 (ADAM10)は、HRS細胞の生存に必要なNotchシグナルを調節する機能の他に、CD30や複数のサイトカインの分泌調整を行うproteinaseの一種である。本研究はHodgkinリンパ腫がADAM10とその基質分子を介して構築する癌微小環境における分子機構の解明で、近年の癌微小環境を標的とした分子標的療法や免疫チェックポイント阻害剤の進歩に貢献する可能性がある。Hodgkinリンパ腫はAYA世代に発生する稀少癌で、治療上の社会的意義が大きい。