Exploring the cell biology, tumor immunology and clinical significance of IL17RB in breast cancer

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K18073
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Japanese Foundation for Cancer Research (2020-2021); Okinaka Memorial Institute for Medical Research (2019)
• Principal Investigator: OZAKI Yukinori 公益財団法人がん研究会, 有明病院 乳腺内科, 副医長 (60756683)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 乳癌 / EMT / IL17RB / IL33 / FSTL1 / 腫瘍免疫

Outline of Final Research Achievements

To explore the way to overcome metastatic or recurrent breast cancer, we conducted research to clarify the significance of IL17RB expression in breast cancer. We have established a cell line with forced expression of IL17RB, which induces EMT and releases IL33 in response to 5FU therapy. And we found this cell induced mast cell infiltration and promoted tumor growth. Analysis of tumor tissues of breast cancer suggested that tumor cells with high IL17RB expression have high invasive potential and is associated with poor outcome of disease-free survival. These findings suggest the clinical significance of targeting the IL17RB-IL33 axis in breast cancer therapy and may contribute to improving outcomes of breast cancer.

Free Research Field

腫瘍内科

Academic Significance and Societal Importance of the Research Achievements

早期/局所進行乳癌の約3割は再発をきたし、転移再発乳癌は依然として根治不能である。その背景には、がんの上皮間葉転換 (EMT)やEMTs制御機構が関わっていると考えられる。乳癌においてIL17RBがEMTや再発にどのように関わっているかを解明することで、乳癌の再発抑制、再発後の転移制御を目指した治療開発が可能となり、乳癌再発の低下や長期生存を目指すことができるようになる。今回我々は、IL17RBが乳癌細胞のEMTを惹起する予後不良因子であり、それを克服するためのIL17RB-IL33軸を標的とした治療開発の臨床的意義を提示することができた。