Elucidation of the maturation mechanism and clinical significance of TLS after esophageal cancer NAC by IMC

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K16490
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Kyushu University
• Principal Investigator: KIBE Shin 九州大学, 医学研究院, 共同研究員 (00910605)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 食道癌 / TLS / 腫瘍免疫微小環境 / scRNA-seq

Outline of Final Research Achievements

In recent years, the indication for immune checkpoint inhibitors has expanded for esophageal cancer. However, the response rate remains low, and there is a need to elucidate the heterogeneity of the tumor immune microenvironment (TIME) that contributes to this therapeutic resistance. Traditionally, anti-tumor immunity was believed to involve dendritic cells presenting tumor-specific antigens in secondary lymphoid organs such as lymph nodes. However, recent findings suggest that tertiary lymphoid structures (TLS) within the tumor area can perform similar functions. In our study, we investigated the correlation between the presence of TLS and prognosis, and elucidated the functional heterogeneity of TIME using single-cell RNA sequencing (scRNA-seq).

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

近年は、腫瘍局所におけるTLSが予後因子として報告されているが、その臨床学的に与える影響の機序や分子生物学的な詳細を報告したものは無く、TLSと抗腫瘍免疫における機能的な関与は不明であった。今回我々が行ったscRNAseqにより、TLSが腫瘍免疫微小環境（TIME）に与える機能的な変化が明らかとなった。本研究成果が新規食道癌治療開発に繋がることが期待され、さらにこの新たなアプローチは他の固形癌にも応用可能であり、学術的にも社会的にもインパクトの大きい研究と言える。