Gu Fenfen, Hu Chuling, Li Chao
Department of Clinical Pharmacy, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, No. 1665 Kongjiang Road, Yangpu District, Shanghai, 200092, PR China.
Discov Oncol. 2025 Aug 5;16(1):1475. doi: 10.1007/s12672-025-03358-6.
Breast cancer can be classified based on HER2 status into HER2-positive (HER2+) and HER2-negative (HER2-) subtypes, which differ significantly in pathogenesis, prognosis, and treatment response. Immune cells are critical components of the tumor microenvironment, influencing breast cancer progression. However, their specific roles in HER2 + and HER2- breast cancer subtypes are not yet fully understood.
This study applied Mendelian randomization (MR) analysis to investigate causal relationships between 731 immune cell phenotypes and breast cancer with different HER2 statuses. Genetic data were obtained from the Finngen and OPENGWAS databases. Inverse variance weighted (IVW) analysis and sensitivity tests were used to ensure the robustness of results.
Our analysis revealed significant associations between specific immune cell traits and breast cancer subtypes. For instance, B cell traits such as "Sw mem %B cell" and "IgD- CD38- %B cell" were positively correlated with the development of HER2 + breast cancer. Conversely, traits associated with T cell maturation and myeloid cells demonstrated a negative correlation with HER2 + breast cancer. Regulatory T cell traits were more strongly linked to HER2- breast cancer.
Distinct immune cell profiles are associated with HER2 + and HER2- breast cancers. These findings provide insights into the immunological differences between subtypes and suggest potential targets for personalized immunotherapy strategies. Further research is required to clarify underlying mechanisms.
乳腺癌可根据人表皮生长因子受体2（HER2）状态分为HER2阳性（HER2+）和HER2阴性（HER2-）亚型，这两种亚型在发病机制、预后和治疗反应方面存在显著差异。免疫细胞是肿瘤微环境的关键组成部分，影响乳腺癌的进展。然而，它们在HER2+和HER2-乳腺癌亚型中的具体作用尚未完全明确。
本研究应用孟德尔随机化（MR）分析来探究731种免疫细胞表型与不同HER2状态乳腺癌之间的因果关系。基因数据来自芬兰基因数据库（Finngen）和开放全基因组关联研究数据库（OPENGWAS）。采用逆方差加权（IVW）分析和敏感性检验以确保结果的稳健性。
我们的分析揭示了特定免疫细胞特征与乳腺癌亚型之间的显著关联。例如，“Sw mem%B细胞”和“IgD-CD38-%B细胞”等B细胞特征与HER2+乳腺癌的发生呈正相关。相反，与T细胞成熟和髓系细胞相关的特征与HER2+乳腺癌呈负相关。调节性T细胞特征与HER2-乳腺癌的联系更为紧密。
不同的免疫细胞谱与HER2+和HER2-乳腺癌相关。这些发现为亚型之间的免疫差异提供了见解，并为个性化免疫治疗策略提出了潜在靶点。需要进一步研究以阐明潜在机制。
