Deciphering the role of LGALS2: insights into tertiary lymphoid structure-associated dendritic cell activation and immunotherapeutic potential in breast cancer patients

IF 27.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Cancer Pub Date : 2024-09-30 DOI:10.1186/s12943-024-02126-4

Shuyu Li, Nan Zhang, Hao Zhang, Zhifang Yang, Quan Cheng, Kang Wei, Meng Zhou, Chenshen Huang

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Abstract

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.

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解密 LGALS2 的作用：洞察乳腺癌患者的三级淋巴结构相关树突状细胞激活和免疫治疗潜力

癌症研究的最新进展突显了三级淋巴结构（TLS）在调节免疫反应中的关键作用，尤其是在乳腺癌（BRCA）中。在这里，我们利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，并确定 LGALS2 是 TLSs 中的一个关键标记。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（DCs）刺激中的作用，并揭示了肿瘤微环境（TME）在宏观和微观层面的复杂性。LGALS2 表达的升高与生存期的延长有关，而生存期的延长与以多样化免疫细胞浸润和活跃的抗肿瘤通路为特征的强健免疫反应有关，这导致了 "热 "肿瘤微环境。苏木精-伊红（HE）、免疫组织化学（IHC）和体内验证分析证实了LGALS2与TLS相关DC的共定位及其在BRCA免疫激活中的作用。将 LGALS2 鉴定为 BRCA 的一个关键因素，不仅凸显了它在新型 TLS 引导的免疫疗法中的治疗潜力，还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。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Cancer 医学-生化与分子生物学

CiteScore

54.90

自引率

2.70%

发文量

224

审稿时长

2 months

期刊介绍： Molecular Cancer is a platform that encourages the exchange of ideas and discoveries in the field of cancer research, particularly focusing on the molecular aspects. Our goal is to facilitate discussions and provide insights into various areas of cancer and related biomedical science. We welcome articles from basic, translational, and clinical research that contribute to the advancement of understanding, prevention, diagnosis, and treatment of cancer. The scope of topics covered in Molecular Cancer is diverse and inclusive. These include, but are not limited to, cell and tumor biology, angiogenesis, utilizing animal models, understanding metastasis, exploring cancer antigens and the immune response, investigating cellular signaling and molecular biology, examining epidemiology, genetic and molecular profiling of cancer, identifying molecular targets, studying cancer stem cells, exploring DNA damage and repair mechanisms, analyzing cell cycle regulation, investigating apoptosis, exploring molecular virology, and evaluating vaccine and antibody-based cancer therapies. Molecular Cancer serves as an important platform for sharing exciting discoveries in cancer-related research. It offers an unparalleled opportunity to communicate information to both specialists and the general public. The online presence of Molecular Cancer enables immediate publication of accepted articles and facilitates the presentation of large datasets and supplementary information. This ensures that new research is efficiently and rapidly disseminated to the scientific community.