Delopment of Innovative Therapy via Interaction between C5aR and PD-L1 Inhibitors in Hepatocellular Carcinoma

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K15529
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Kumamoto University
• Principal Investigator: Kaida Takayoshi 熊本大学, 大学院生命科学研究部(医), 特定研究員 (80792580)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 肝細胞癌 / C5aR

Outline of Final Research Achievements

Immunostaining expression analysis in clinical specimens was performed to evaluate nutritional status and prognostic associations. PD-L1 and PD1 in tumors were significantly inversely correlated, and PD-L1-positive patients had significantly worse recurrence-free survival. C5aR expression was confirmed in clinical specimens by immunostaining. In vitro, we co-cultured a liver stromal cell line with LX2, which expresses high levels of C5aR, and HLF and HLE, which are hepatocellular carcinoma cell lines that express low levels of C5aR. with recombinat C5aR, HLE and HLF showed no increase in proliferative ability, but significant increase in invasive ability.

Free Research Field

消化器系悪性腫瘍

Academic Significance and Societal Importance of the Research Achievements

肝細胞癌は未だ難治性の消化器癌の1つであり有効な抗がん剤は数少なく、効果も乏しいのが現状である。近年新しく開発された免疫チェックポイント阻害剤の恩恵を受けられる症例が少しずつ報告されて脚光を浴びている。肝細胞癌においてPD-L1陽性症例は、無再発生存期間が有意に不良であった。PD1/CD8が低いほど無再発生存期間が有意に不良であることがわかった。さらにフレイルの人は有意に腫瘍内PD-L1 陽性症例の割合が高いことが判明した。