Elucidation of PD-L1 functions under genotoxic condition

2019 Fiscal Year Final Research Report

• Project/Area Number: 19K21268
• Project/Area Number (Other): 18H06157 (2018)
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund (2019); Single-year Grants (2018)
• Review Section: 0901:Oncology and related fields
• Research Institution: Tohoku University
• Principal Investigator: NIHIRA NAOE 東北大学, 歯学研究科, 大学院非常勤講師 (40589470)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: PD-L1

Outline of Final Research Achievements

Almost tumor cells are eliminated by the immune system, including T lymphocytes and natural killer cells. However, many types of tumor cells acquire the immune tolerance by inhibiting T-cell activation and functions. To this end, PD-L1 is identified to function as a ligand for PD-1, which is the receptor of the immunoglobulin superfamily expressing on the cell surface of T-cells. Translocation of PD-L1 into the nucleus from plasma membrane have been reported, however, the regulatory mechanisms for it remain largely unclear. In this project, we clarified the molecular basis for nuclear translocation of PD-L1. Furthermore, we found that the nuclear translocation is regulated by PD-L1 acetylation.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

本研究によって、我々はPD-L1の脱アセチル化が核内移行の制御因子との結合を促し、核内移行を引き起こすことを明らかにした。そして、脱アセチル化酵阻害剤を細胞に処理すると核内移行が抑制されることを明らかにした。マウスを用いた解析では、脱アセチル化酵素阻害剤を抗PD-1治療薬と共に投与することで、抗PD-1治療薬による抗腫瘍効果が認められた。こ