Deciphering the dynamic immune microenvironment in gastric cancer with peritoneal metastasis to identify novel Immunotherapeutic targets and biomarkers

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K15586
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Kumamoto University
• Principal Investigator: Yamashita Kohei 熊本大学, 大学院生命科学研究部(医), 特定研究員 (00867202)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 胃癌 / 腹膜播種 / 腫瘍免疫微小環境 / サブクローン

Outline of Final Research Achievements

Immunotherapies such as immune checkpoint inhibitors have been clinically applied based on effective results in clinical trials for gastric cancer. However, their efficacy against gastric cancer peritoneal metastasis, the most common form of metastasis in gastric cancer, remains limited. There is a pressing need to elucidate the tumor immune microenvironment specific to gastric cancer peritoneal metastasis.
This study analyzed gastric cancer ascites cells and identified a subpopulation of cells in the ascitic fluid that exhibit characteristics of both gastric cancer cells and myeloid cells. Using biostatistical methods, a phylogenetic analysis of cells in the ascitic fluid was conducted. The analysis suggested a linear evolutionary lineage rather than a branching one, and a group of genes potentially involved in this lineage was identified. Future work will involve detailed functional analysis of the identified cell subpopulations and gene groups.

Free Research Field

腫瘍生物学、消化器外科学

Academic Significance and Societal Importance of the Research Achievements

進行胃がんのうち、腹膜播種は治療抵抗性であり予後不良である。近年のがん免疫治療の進歩は胃がんの予後向上に資する可能性があり、腹膜播種の腫瘍免疫微小環境の解明は、新規治療標的や治療効果予測のバイオマーカー創出につながる。本研究により、胃がん腹膜播種における進化系統やそれに関与する遺伝子変異群が推定された。今後、胃がん腹膜播種の進行を食い止めるための免疫治療の役割がクローズアップされることが期待される。