Development of a novel prognostic marker for pancreatic cancer chemotherapy as an indicator of MDSC reduction due to myelosuppression.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16081
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Gifu Pharmaceutical University
• Principal Investigator: Fujii Hironori 岐阜薬科大学, 薬学部, 客員共同研究員 (90775173)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 重篤な好中球減少 / MDSC / がん化学療法 / 生存期間 / フローサイトメトリー解析 / 不死時間バイアス / 時間依存性Cox回帰分析

Outline of Final Research Achievements

Patients with severe neutropenia may have decreased myeloid derived suppressor cells (MDSC), which may be an indicator of the efficacy of anticancer drugs.
First, to establish a system for measuring MDSC concentration, we investigated conditions using three types of cultured human leukemia cells, HL60, NB4, and KG-1, and were able to isolate all cells as CD11b+CD14- CD33+ by flow cytometry analysis. In addition, severe neutropenia was used as a surrogate marker of MDSC decline and its association with overall survival (OS) was examined. Time-dependent Cox regression analysis with immortality time bias was performed in patients treated with trifluridine tipiracil hydrochloride and bevacizumab. Results showed that severe neutropenia was significantly associated with prolonged OS.

Free Research Field

臨床薬剤学

Academic Significance and Societal Importance of the Research Achievements

本研究では、骨髄由来免疫抑制細胞(MDSC)濃度測定系の確立を行ったのちに、トリフルリジンチピラシル塩酸塩とベバシズマブ併用療法の重篤な好中球減少をMDSCの低下のサロゲートマーカーと仮定し、治療効果との関連を検討した。本研究で、ヒト検体を用いてMDSCを測定することはコロナ禍でできなかったが、時間依存性COX回帰分析を用いて、重篤な好中球減少と治療効果との関連を明らかにできたことで、重篤な好中球減少を指標にしたがん化学療法の治療効果予測の可能性を高めることにつながった。今後ヒト検体を用いて、MDSC濃度を調べることで治療効果の向上に大きく貢献できるものと考える。