An analysis on the function of tumor vascular endothelial cells as a switch controlling the immune set point

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08891
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55040:Respiratory surgery-related
• Research Institution: Saitama Medical University
• Principal Investigator: Hato Tai 埼玉医科大学, 医学部, 准教授 (10365281)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: がん微小環境 / 腫瘍血管内皮細胞 / 肺癌 / がん免疫 / VEGF / VEGFR2

Outline of Final Research Achievements

Our hypothesis is that vascular endothelial cells induced by pathological angiogenesis in cancer tissues may be hijacked to suppress antitumor immunity through direct and indirect actions of cancer cells. We attempted to clarify their involvement from in vivo and clinical pathological aspects. In animal experiments, tumors created using a subcutaneous tumor transplantation model in mice were excised and isolated into single-cell suspensions, and then CD31-positive cells were depleted using a magnetic bead method, and the tumor growth was compared in a model in which the cells were re-transplanted into a different mouse. In addition, we used human lung cancer specimens to compare the relationship between vascular structure and microvessel density, tumor microenvironment, and survival.

Free Research Field

呼吸器外科

Academic Significance and Societal Importance of the Research Achievements

がんの免疫療法を高める方法として、腫瘍血管機能を正常化する抗血管新生療法との併用療法が提案されている。実際に、肝細胞癌では免疫チェックポイント療法と抗VEGF/VEGFR2抗体の併用療法は有用な治療方法である。そのメカニズムとして、血管構築が正常化した結果、がん微小環境の改善がえられて免疫応答が改善する可能性が示唆されている。本研究では、治療介入のない腫瘍の血管内皮細胞は一見正常であっても機能的には免疫応答を維持する機能は欠けている可能性を示唆している。抗VEGF/VEGFR2抗体による免疫応答改善は、微小環境改変よりも直接的な免疫応答改善機能の影響が強いと推察される。