Development of a novel therapeutic strategy for PTCL-NOS based on functional analysis of tumor microenvironment

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17403
• 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: Kagoshima University
• Principal Investigator: Sugio Takeshi 鹿児島大学, 医歯学総合研究科, 特別研究員PD (10870446)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 末梢性T細胞リンパ腫 / 微小環境 / 遺伝子発現解析 / イメージングマスサイトメトリー / cfDNA

Outline of Final Research Achievements

Gene expression analysis of peripheral T-cell lymphoma (PTCL) tumor tissues showed that the patients could be classified into four groups according to microenvironment-related gene expression, and the Macrophage-rich and NME groups (low expression of B-cell and dendritic cell-related genes) had a poor prognosis. Macrophage-rich cases had high expression level of PD-L1 and NME patients had high expression level of BIRC5. BIRC5 inhibition by inhibitor and gene modification was effective in inhibiting tumor growth in both in vitro and vivo disease models. After microenvironmental profiling of a few cases by imaging mass cytometry, we noticed a large heterogeneity in the same cases and within the same tissues. As a result, we developed a comprehensive evaluation method of immune microenvironment using cfDNA.

Free Research Field

血液腫瘍分野

Academic Significance and Societal Importance of the Research Achievements

本研究において、PTCLという希少かつ予後不良な疾患が微小環境関連遺伝子発現によって分類でき、予後層別化できることを検証した。さらにその分類に基づいた予後不良症例に対する新規治療標的の候補も同定した。今後の臨床試験の計画、予後改善のために有用であることから意義深いと考えられる。さらに、cfDNAを用いた微小環境評価法の開発を行なっているが、非侵襲的にかつ経時的に評価可能な系であり、社会的意義も大きいと考えられる。