Development of novel therapeutic strategies targeting the tumor immune microenvironment of breast cancer liver metastases.

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K15530
• 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): 2021-04-01 – 2023-03-31
• Keywords: 乳癌 / 腫瘍免疫微小環境 / 肝転移

Outline of Final Research Achievements

In patients with metastatic breast cancer, the control of liver metastasis, which is strongly associated with prognosis, is essential and represents a significant challenge in breast cancer treatment. Utilizing a mouse breast cancer liver metastasis model, we observed that the effect of immune checkpoint inhibitors on breast cancer liver metastasis was limited, with notably reduced tumor infiltration by CD8-positive cells compared to the primary tumor. Additionally, in the 4T1 tumor-bearing mice, we confirmed a significant increase in neutrophil infiltration in hepatocytes through immunohistochemistry, flow cytometry, and transcriptome analysis. These findings contribute to elucidating the causal relationship between breast cancer and the hepatic immune microenvironment and significantly enhance our understanding of breast cancer liver metastasis, which may have implications for future therapeutic strategies.

Free Research Field

乳癌の腫瘍免疫微小環境

Academic Significance and Societal Importance of the Research Achievements

転移を有する乳癌患者の約70%が肝転移を有するといわれており、患者のQOL並びに医療経済双方の観点から、肝転移に対する治療戦略を検討することは、早急に取り組むべき大きな課題である。本研究成果において、肝臓に転移浸潤した腫瘍細胞のみならず、担癌状態であることが既に肝臓における腫瘍免疫微小環境の形成に関わっている事が明らかになった。全身性の宿主免疫応答が各臓器別に生じていることは、今後の乳癌肝転移制御という観点から、非常に重要な知見であると考える。