Recent advances in cancer research have highlighted the pivotal role of tertiary lymphoid structures (TLSs) in modulating immune responses, particularly in breast cancer (BRCA). Here, we performed an integrated analysis of bulk transcriptome data from over 6000 BRCA samples using biological network-based computational strategies and machine learning (ML) methods, and identified LGALS2 as a key marker within TLSs. Single-cell sequencing and spatial transcriptomics uncover the role of LGALS2 in TLS-associated dendritic cells (DCs) stimulation and reveal the complexity of the tumor microenvironment (TME) at both the macro and micro levels. Elevated LGALS2 expression correlates with prolonged survival, which is associated with a robust immune response marked by diverse immune cell infiltration and active anti-tumor pathways leading to a ‘hot’ tumor microenvironment. The colocalization of LGALS2 with TLS-associated DCs and its role in immune activation in BRCA were confirmed by hematoxylin-eosin (HE), immunohistochemistry (IHC), and in vivo validation analyses. The identification of LGALS2 as a key factor in BRCA not only highlights its therapeutic potential in novel TLS-directed immunotherapy but also opens new avenues in patient stratification and treatment selection, ultimately improving clinical management.

中文翻译：

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解读 LGALS2 的作用：深入了解乳腺癌患者三级淋巴结构相关的树突状细胞激活和免疫治疗潜力


癌症研究的最新进展强调了三级淋巴结构 (TLS) 在调节免疫反应中的关键作用，特别是在乳腺癌 (BRCA) 中。在这里，我们使用基于生物网络的计算策略和机器学习 (ML) 方法对来自 6000 多个 BRCA 样本的大量转录组数据进行了综合分析，并将 LGALS2 确定为 TLS 中的关键标记。单细胞测序和空间转录组学揭示了 LGALS2 在 TLS 相关树突状细胞 (DC) 刺激中的作用，并揭示了宏观和微观层面上肿瘤微环境 (TME) 的复杂性。 LGALS2 表达升高与生存期延长相关，这与强大的免疫反应有关，其特征是多样化的免疫细胞浸润和活跃的抗肿瘤途径，导致“热”肿瘤微环境。 LGALS2 与 TLS 相关 DC 的共定位及其在 BRCA 免疫激活中的作用通过苏木精-伊红 (HE)、免疫组织化学 (IHC) 和体内验证分析得到证实。 LGALS2 被鉴定为 BRCA 的关键因素，不仅凸显了其在新型 TLS 导向免疫疗法中的治疗潜力，而且为患者分层和治疗选择开辟了新途径，最终改善了临床管理。