Reprogramming of breast cancer liver metastasis microenvironment by inducible nitric oxide synthase regulation

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K16770
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Kyoto University
• Principal Investigator: Kawaguchi Kosuke 京都大学, 医学研究科, 助教 (30516927)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 腫瘍免疫微小環境 / 乳がん / 肝転移

Outline of Final Research Achievements

The limited efficacy of cancer immunotherapy in breast cancer liver metastases is a problem. In this study, we analyzed the tumor immune microenvironment of breast cancer liver metastases using a mouse model of breast cancer liver metastases and human clinical samples. We found that liver metastases did not respond well to treatment compared to primary tumors and lung metastases. Furthermore, comprehensive analysis of gene expression patterns in liver metastases suggested that they are associated with distinct immune and metabolic pathways, such as the complement pathway. These results suggest that liver metastases from breast cancer can be controlled by reprogramming the tumor immune microenvironment, specifically in liver metastases.

Free Research Field

腫瘍免疫微小環境

Academic Significance and Societal Importance of the Research Achievements

本研究により、肝転移巣特異的な腫瘍免疫微小環境形成に補体経路が関わる事が示唆された。肝転移の制御は乳癌患者の生存のみならず生活の質に大きく関わる為、非常に重要な社会的意義を持つ。今後の継続研究により、肝転移巣の腫瘍免疫微小環境をターゲットとした治療ストラテジーの開発が急務であると考える。