Elucidation of diversity and novel roles of APCs in the cancer microenvironment by scRNAseq with spatial gene expression analysis

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K19530
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 55:Surgery of the organs maintaining homeostasis and related fields
• Research Institution: Kyushu University
• Principal Investigator: OHUCHIDA Kenoki 九州大学, 医学研究院, 准教授 (20452708)
• Co-Investigator(Kenkyū-buntansha): 木庭 遼 九州大学, 医学研究院, 共同研究員 (10866776) ; 小薗 真吾 九州大学, 医学研究院, 共同研究員 (40706850) ; 三好 圭 九州大学, 医学研究院, 共同研究員 (70755272)
• Project Period (FY): 2021-07-09 – 2023-03-31
• Keywords: 消化器癌 / 腫瘍微小環境 / 抗原提示細胞 / B細胞 / 樹状細胞 / 食道癌 / scRNA-seq

Outline of Final Research Achievements

Recently, tertiary lymphoid structures (TLS) have been reported to be involved in anti-tumor immunity in the tumor microenvironment, and B cells, which are one of the antigen-presenting cells (APCs), play an essential role in TLS formation. The present study investigated the significance and role of TLS in esophageal squamous-cell carcinoma (ESCC). As a result, the presence and maturity of TLS in ESCC were significantly correlated with better prognosis. In cases with a high number of TLS, dendritic cells, which are APCs, were significantly more abundant. Moreover, the present study showed that follicular helper T cells in TLS may activate dendritic cells. In the future, we are planning to use spatial gene expression analysis (Visium) to evaluate the intercellular interactions between TLS and APCs in the tumor microenvironment.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

近年、scRNA-seqを用いた腫瘍微小環境の解明が急速に進んでおり、これまで判明していなかった細胞集団や遺伝子発現に基づいた分類が報告されている。腫瘍免疫の分野ではAPCの多様性が示唆されているものの、一定の見解はなく、ヒト腫瘍微小環境中のAPCの局在や機能的差異、そして他の細胞種との相互作用についての報告は少ない。本研究により消化器癌における、APCを中心とした腫瘍免疫メカニズムの理解が深まることで、免疫療法の新たな治療アプローチの可能性を生み出す礎になる可能性がある。