Anti-angiogenic and lymphangiogenic therapy improves the tumor microenvironment and enhances the effectiveness of immunotherapy

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K08133
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Tohoku University
• Principal Investigator: Okazaki Tatsuma 東北大学, 大学病院, 講師 (40396479)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: リンパ管 / がん免疫療法 / 血管 / 癌微小環境

Outline of Final Research Achievements

In this study, we identified a previously unknown normal anatomy of lymphatics and blood vessels in the pleura covering the mouse chest wall and diaphragm. We immuno-stained the chest wall and diaphragm with markers for lymphatics and blood vessels. We observed and identified and their anatomy using a microscope.
Lymphatics include initial and collecting lymphatics. We identified their distribution in the pleura. We also confirmed the distribution of blood vessel networks of arteries, veins, and capillaries in the pleura. Next, we developed a disseminated metastatic mouse tumor model on the pleura of the chest wall and diaphragm. We immuno-stained this model with lymphatic and blood vessel markers. We were able to clearly observe the flowing out lymphatics and flowing in blood vessels of each tumor using a microscope. In this model, each tumor was small, and lymphangiogenesis and angiogenesis from the surrounding vasculatures to the tumor could be identified.

Free Research Field

呼吸器内科学

Academic Significance and Societal Importance of the Research Achievements

癌や肺炎等の合併症に胸水貯留がある。胸水は肺を圧排し呼吸苦等を引き起こし患者さんの予後を悪化させる。胸水は胸膜の血管から産生されリンパ管から排出される。しかし、胸膜のリンパ管や血管の正常解剖、及び癌による病理学的変化はこれまで不明だった。本研究はこれらの不明な点を同定し、新規胸水対策の可能性を示した。また、本腫瘍モデルでは明瞭に脈管系を観察できるため、免疫細胞の腫瘍リンパ管や血管への分布を観察できる。癌免疫療法の効果を確認する際に、本モデルは腫瘍と脈管における免疫細胞の分布の確認を可能とした。