Identification of tumor-associated macrophages promoting early-stage metastasis during peritoneal dissemination in gastric cancer

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20841
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: Kanagawa Cancer Center Research Institute
• Principal Investigator: Kawase Wataru 地方独立行政法人神奈川県立病院機構神奈川県立がんセンター(臨床研究所), 臨床研究所がん治療学部, 研究員 (70966605)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: 腹膜播種 / 胃癌 / 腫瘍関連マクロファージ / 転移

Outline of Final Research Achievements

Peritoneal dissemination (PD) is the most frequent metastasis pattern in gastric cancer (GC) and is a significant predictor of poor prognosis. However, the mechanisms underlying PD formation remain unclear, and a PD-specific signature has not been identified. PD development is thought to be influenced by various changes occurring in GC tumor cells and immune cells present in the peritoneal cavity. In this study, we aimed to identify the specific cell type responsible for promoting metastasis during the early stage of PD in GC. We demonstrated the abundant presence of tumor-associated macrophages (TAMs) in CY1 GC ascites using flow cytometry analysis and identified several genes that were significantly expressed in CY1 TAMs using single-cell RNA-seq analysis. Furthermore, we evaluated the potential of these genes to serve as therapeutic targets for the treatment of PD in GC.

Free Research Field

腫瘍学

Academic Significance and Societal Importance of the Research Achievements

胃癌腹膜播種は極めて予後不良であるが、腹膜播種形成のメカニズムは不明であり、有効な治療法の確立されていない。胃癌腹膜播種転移の初期過程において、どのようなTAMがPro-tumorに機能し、がん細胞と相互作用しているのかという問いを解明することで術後腹膜播種再発の予測因子や免疫チェックポイント阻害薬に関するバイオマーカーの探索に有用なだけでなく、胃癌腹膜播種に対する画期的な新規治療薬の開発にも繋がると考えられる。