Tumor Microenvironment Analysis of germ-line BRCA mutated Triple Negative Breast Cancer

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K16463
• 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: Okayama University
• Principal Investigator: Takahashi Yuko 岡山大学, 大学病院, 講師 (90892191)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 乳がん / トリプルネガティブ

Outline of Final Research Achievements

This study aimed to evaluate the immune response in the tumor microenvironment to predict the therapeutic effect of immune checkpoint inhibitors against triple-negative breast cancer (TNBC). In TNBC, we investigated the involvement of B cells and tertiary lymphoid tissue-like structures in anti-tumor activity, which have been reported in recent years in several other malignant tumors but not in breast cancer. In TNBC, pre-B-cell leukemia homeobox 4 (PBX4), which is involved in cell infiltration and has been reported to be correlated with prognosis in several malignant tumors, and killer cell immunoglobulin-like receptor 3 Ig domains and short cytoplasmic tail 1 (KIR3DS1), which has been reported to have reduced NK cell function and resistance to ICI therapy due to mutations, were highly expressed in TNBC. Furthermore, PBX4 was also highly expressed in BRCA-positive BC.

Free Research Field

乳腺内分泌外科

Academic Significance and Societal Importance of the Research Achievements

近年免疫チェックポイント阻害剤（ICI）はトリプルネガティブ乳がん（TNBC）の標準治療の一つとして位置付けられており、PD-L1等以外の治療効果を予測するバイオマーカーの同定が期待されている。本研究ではTNBCの微小環境において、三次リンパ組織様構造を構成するT・Bリンパ球等免疫関連細胞の遺伝子群の発現を検討した。TNBCの微小環境において、PBX4やKIR3DS1などが関与する免疫応答細胞の関与が示唆された。今後症例数を増やしたvalidation studyが必要であるが、本研究の結果は、本邦におけるICI既治療例の治療効果を予測するバイオマーカーの同定に有用であると考えられる。