Elucidating the nature of primary central nervous system lymphoma based on the microenvironment and exploring new therapeutic targets

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09106
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: National Institute of Infectious Diseases (2023); Yokohama City University (2021-2022)
• Principal Investigator: Nishi Mayuko 国立感染症研究所, ウイルス第三部, 主任研究官 (90635343)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 脳腫瘍 / 悪性リンパ腫 / 微小環境 / 細胞間相互作用 / ペリサイト

Outline of Final Research Achievements

Primary central nervous lymphoma (PCNSL) is a malignant lymphoma that is confined to the central nervous system and does not involve other organs, with rapid progression and a poor long-term prognos. Although PCNSL is a clinically serious malignant tumor, the detailed molecular mechanisms of its origin and proliferation/invasion have not yet been elucidated. This is due to the fact that PCNSL requires a specific microenvironment for growth, which has not been achieved in in vitro culture systems. We have successfully established an in vitro culture system that maintains the minimum microenvironment required for PCNSL survival by using ad-MED vitrigel with a collagen vitrigel membrane as an insert, to double-side-culture PCNSL cells from patients and cerebrovascular-derived pericytes. Using this co-culture system, we identified several signaling pathways and subsequent phosphorylation signaling factors that are important for the proliferation and progression of PCNSL.

Free Research Field

脳神経外科学

Academic Significance and Societal Importance of the Research Achievements

従来PCNSL研究は、患者腫瘍組織を免疫不全マウス脳内に移植した”Orthotopic(同所性)”PDX（patient-derived xenograft）が、生体外で腫瘍細胞を増殖できる唯一の方法として活用されてきた。しかしながら、PDXは腫瘍細胞以外の細胞群がマウス由来細胞であること、生きたマウス脳内に細胞を移植するための労力や費用が負担になること、一細胞レベルの解析やハイスループットの薬剤スクリーニングには適さないことなどがネックになっていた。我々が構築したPCNSL-ペリサイト両面培養系により諸問題が解決され、PCNSLの新規治療法開発に向けた基盤研究が促進されることが期待できる。