targeting therapy of immunocheckpoint in HER2 positive breast cancer

Research Project

Project/Area Number	15K10053
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	General surgery
Research Institution	Department of Clinical Research, National Hospital Organization Kure Medical Center (2016-2017) Hiroshima University (2015)
Principal Investigator	Shigematsu Hideo 独立行政法人国立病院機構(呉医療センター臨床研究部), その他部局等, その他 (40543707)
Co-Investigator(Kenkyū-buntansha)	岡田守人広島大学, 原爆放射線医科学研究所, 教授 (70446045)
Research Collaborator	OZAKI Shinji
Project Period (FY)	2015-04-01 – 2018-03-31
Project Status	Completed (Fiscal Year 2017)
Budget Amount *help	¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000) Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords	breast / HER2 / Treg / PD-L1 / 乳癌 / Tregの機能解析 / Immune checkpoint
Outline of Final Research Achievements	1. Tumor infiltrating lymphocyte was extracted using gentle MACS Dissociator from specimens of core needle biopsy in HER2 positive breast cancer who underwent neoadjuvant chemotherapy. Functional assay of Treg was performed by flow cytometry using fluorescent anti-body for CD4, CD4, CD45RA and FOXP3. In breast cancer tissue, proportion of functional Treg was significantly higher than proportions in PBMC and normal breast tissue. Fraction of Treg was significantly lower in pCR population then in non pCR population (25.1% vs. 29.3%, p = 0.044). 2. Expression of PD-L1 in HER2 positive breast cancer was evaluated using auto staining system and semi-quanitative immunohistochemical analysis. The proportion of PD-L1 positive (>1%) was 35%, and there was tendency of better relapse-free survival in patients with PD-L1 positive breast cancer compared with those with PD-L1 negative breast cancer.