Efficacy of immune checkpoint blockade for Epstein-Barr virus-associated gastric carcinoma

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07974
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Yamaguchi University
• Principal Investigator: Nishikawa Jun 山口大学, 大学院医学系研究科, 教授 (00379950)
• Co-Investigator(Kenkyū-buntansha): 末廣 寛 山口大学, 大学院医学系研究科, 准教授 (40290978)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: EBウイルス関連胃癌 / 免疫チェックポイント分子 / ニボルマブ

Outline of Final Research Achievements

The overexpression of PD-L1 is one of the features of EBV-associated gastric cancer (EBVaGC); however, the function of PD-L1 has not been studied in EBVaGC. We used three EBVaGC cell lines, SNU719 cells, NCC24 cells, and YCCEL1 cells, to evaluate the PD-L1 expression and function in EBVaGC. Jurkat T-lymphocytes expressing PD-1 were co-cultured with NCC24 and YCCEL1 cells and the cell cycles were analyzed. All of the EBVaGC cell lines expressed PD-L1, and its expression was further enhanced by stimulation with IFN-γ. In Jurkat T-cells co-cultured with IFN-γ-stimulated NCC24 and YCCEL1 cells, the number of cells in the G0/G1 phase was significantly increased. This G0/G1 arrest was partially released by administration of anti-PD-L1 antibody. EBVaGC cells expressing high levels of PD-L1 suppress T-cell proliferation, and the IFN-γ signaling pathway is involved in the expression of PD-L1.

Free Research Field

消化器内科

Academic Significance and Societal Importance of the Research Achievements

EBウイルス関連胃癌はリンパ球浸潤癌の組織型を呈し、PD-L1の発現が高いことが報告されていたが、実際にEBウイルス関連胃癌において、PD-1とPD-L1の相互作用が機能しているかは不明であった。我々はIFN-γ処理により、PD-L1を高発現させたEBウイルス胃癌細胞株とPD-1を発現するT細胞株を共培養することで、T細胞がGrowth arrestを起こすことを示した。抗PD-L1抗体の効果は限定的であったが、EBウイルス関連胃癌の維持に抑制系の免疫チェックポイント分子が機能を果たしていることを証明できた。