Treatment strategy for tumor microenviroment focused on tumor associated macrophage

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08957
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: The University of Tokushima
• Principal Investigator: MORINE Yuji 徳島大学, 大学院医歯薬学研究部(医学域), 准教授 (60398021)
• Co-Investigator(Kenkyū-buntansha): 池本 哲也 徳島大学, 病院, 特任教授 (20398019) ; 居村 暁 徳島大学, 病院, 特任教授 (90380021)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 腫瘍微小環境 / マクロファージ / 難治性癌 / 免疫逃避

Outline of Final Research Achievements

The purpose of this study was to establish the treatment strategy for tumor microenviroment focused on CAF (cancer associated fibroblast)-TAM (tumor associated macrophage) interaction.
At first, we identified that in the tumor microenvironment, the release of OPN (osteopontin) from TAM was increased, and this upregulated OPN further upregulated the OPN secretion from CAF cultured with TAM-CM (conditioned medium), leading to increased malignancy of cancer. Next, we demonstrated that CAF promoted the M2 polarization of macrophages and the induced TAM by CAF upregulated the PAI-1 secretion via CXCL12 of CAF-CM. Subsequently, PAI-1 produced by TAM enhanced the malignant behavior of cancer.
Consequently, our results suggested that CAF-TAM interaction was correlated with tumor malignancy, the canceling the Cancer cell-CAF-TAM interaction would be a breakthrough for intractable cancer strategy.

Free Research Field

医歯薬学、外科系臨床医学、外科学一般

Academic Significance and Societal Importance of the Research Achievements

癌治療において、癌細胞だけでなく腫瘍内血管新生や免疫不全をターゲットとした腫瘍微小環境に対する集学的治療が展開されているが、それらは癌細胞と脈管構成細胞・免疫担当細胞による単一のクロストークをターゲットとしたもので、依然、腫瘍微小環境の一部を攻略しているにすぎない。本研究における癌自体を包括的に捉えた腫瘍微小環境構築におけるCancer cell-TAM interactionの結果は、特にTAMをターゲットとした難治性癌の治療戦略確立のための一助となる可能性がある。