Molecular regulation mechanisms of immune checkpoints by macrophages in IPF-related lung cancer

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K08511
• 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: University of Tsukuba
• Principal Investigator: Sekine Ikuo 筑波大学, 医学医療系, 教授 (10508310)
• Co-Investigator(Kenkyū-buntansha): 野口 雅之 筑波大学, 医学医療系, 教授 (00198582) ; 鈴木 絢子 東京大学, 大学院新領域創成科学研究科, 准教授 (00770348) ; 鈴木 穣 東京大学, 大学院新領域創成科学研究科, 教授 (40323646) ; 鈴木 敏夫 筑波大学, 医学医療系, 講師 (70771856)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 特発性肺線維症 / 肺癌 / マクロファージ / 免疫チェックポイント / VISTA

Outline of Final Research Achievements

The purpose of this study was to elucidate the role of macrophage immune checkpoints in IPF-associated lung cancer. Single-cell RNA sequencing and spatial omics analysis of human lung cancer samples yielded only biased results due to a noticeable imbalance in lung constituent cells. Analysis with Pulmosphere generated from human lung samples suggested that VISTA (V- domain Ig- containing Suppressor of T cell Activation) was located in the downstream of Thromboxane-Prostanoid Receptor signaling. In lung cancer spheres generated from lung cancer cells, noncancerous epithelial cells, lung fibroblasts, and macrophages isolated from human lung cancer samples, knockout of macrophage VISTA did not alter the number or proliferative potential of lung cancer cells.

Free Research Field

腫瘍内科

Academic Significance and Societal Importance of the Research Achievements

当初想定したIPF合併肺癌の病態におけるVISTAの役割は確定的に示すことは出来なかった。そのため、我々は肺線維症と肺癌の両方の病態を促進する抗原提示細胞のcomponentとして候補に挙がっていたLAMP3 (lysosomal associated membrane protein 3)に研究の軸足を移すことにした。IPF合併肺癌の病態は複雑で、完全解明までの道のりは未だ遠いが、その一つの道筋は得られたと考えている。