Association of autoantibodies to HER2 with tumor microenvironments for humoral immunity and prognosis in patients with breast cancer

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10547
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Osaka University
• Principal Investigator: Shimoda Masafumi 大阪大学, 医学系研究科, 助教 (30644455)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 腫瘍微小環境 / 液性免疫 / 自己抗体

Outline of Final Research Achievements

We have demonstrated that high serum concentration of anti-HER2 autoantibody (HER2-AAb) is associated with favorable outcomes in patients with early-stage breast cancer. In the present study, we investigated the immunological tumor microenvironment in patients with early-stage breast cancer whose serum HER2-AAb was high. Subjects included 33 patients with high levels of serum HER2-AAb and 20 patients with low levels of serum HER2-AAb. The high HER2-AAb group showed significantly longer RFS than the low HER2-AAb group. Cell counts of tumor-infiltrating B cells, plasma cells, and CXCL13-positive lymphocytes in the high HER2-AAb group were significantly greater than those in the low HER2-AAb group. Follicular CD4-positive lymphocytes in the axillary lymph nodes of the high HER2-AAb group were more present than those of the low HER2-AAb group. Thus, our results suggest that humoral immunity was enhanced in the tumor microenvironment of the high HER2-AAb group.

Free Research Field

乳腺外科学

Academic Significance and Societal Importance of the Research Achievements

本研究により、HER2自己抗体高値の患者群においては腋窩リンパ節においてB細胞の成熟が促され、CXCL13陽性リンパ球によってB細胞が原発巣にリクルートされることで液性免疫が活性化されるという一連の機序が明らかとなってきた。この流れが乳癌患者において実際に示された意義は大きい。乳癌は腫瘍の体細胞変異が比較的少なく、腫瘍免疫の関与は限定的と思われてきた。しかし本研究で示唆されたように、液性免疫が乳癌の腫瘍免疫においてポジティブな役割を担うとすると、本研究成果を手掛かりとして、新たな免疫療法の進展が期待される。