Investigation of molecular mechanisms for constitutive IRF4 expression in T-cell malignancies

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02775
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Hokkaido University
• Principal Investigator: Nakagawa Masao 北海道大学, 医学研究院, 助教 (80435859)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 成人T細胞性白血病リンパ腫 / T細胞性リンパ腫 / IRF4 / PD-L1 / CAR-T

Outline of Final Research Achievements

Compound library screening revealed a compound, which can reduce IRF4 protein expression in multiple T-cell lymphoma cell lines, including adult T-cell leukemia lymphoma cell lines. ATACseq analysis was performed to analyze the mechanism of conctitutive IRF4 expression, but no common open chromatin region around the IRF4 locus was found among multiple cases. Tissue microarray analysis of T-cell lymphomas revealed the expression frequency of IRF4 and BATF3 by disease type. PD-L1-CAR-T generated in this project exhibited superior cytotoxic activity against PD-L1 high expressing T-cell lymphoma cells.

Free Research Field

悪性リンパ腫

Academic Significance and Societal Importance of the Research Achievements

成人T細胞性白血病リンパ腫を含む一部のT細胞性リンパ腫細胞に必須の遺伝子であるIRF4の発現制御のメカニズムの一端および発現頻度のを明らかにしたことで、今後の治療法開発へ基盤的治知見となる。抗PD-1抗体で病勢増悪の可能性のある成人T細胞性白血病リンパ腫に対して、PD-L1-CAR-T開発への可能性を示した。