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乳腺癌中异质性癌症相关成纤维细胞亚群与免疫系统之间的串扰:关键参与者和有前景的治疗靶点

Crosstalk between heterogeneous cancer-associated fibroblast subpopulations and the immune system in breast cancer: key players and promising therapeutic targets.

作者信息

Liu Lu, Wan Weijun, Chang Yilin, Ao Luoquan, Xu Yan, Xu Xiang

机构信息

State Key Laboratory of Trauma and Chemical Poisoning, Department of Stem Cell and Regenerative Medicine, Daping Hospital, Army Medical University, Chongqing, 400010, China.

Department of Breast and Thyroid Surgery, Daping Hospital, Army Medical University, Chongqing, 400010, China.

出版信息

J Exp Clin Cancer Res. 2025 Sep 1;44(1):263. doi: 10.1186/s13046-025-03527-z.

Abstract

The tumor microenvironment (TME) of breast cancer is a complex ecosystem, in which cancer-associated fibroblasts (CAFs), as the most abundant stromal cell type, meticulously construct an ecological niche that supports tumor growth through mechanisms including extracellular matrix (ECM) remodeling, secretion of bioactive factors, and interactions with neighboring cells. High-resolution technologies, including single-cell sequencing and spatial transcriptomics, have revealed the high heterogeneity, functional diversity, and spatial distribution within the CAF population. Significant differences exist in the interactions between distinct CAF subpopulations and immune cells. Through complex crosstalk with the immune system, they collaboratively establish an immunosuppressive network, becoming a core driving force for tumor immune escape. This review focuses on the latest research advances in heterogeneous subpopulations of CAFs within the breast cancer microenvironment, delves into how the complex bidirectional crosstalk between different CAF subpopulations and immune cells collaboratively shapes the tumor immune microenvironment (TIME), and summarizes various CAF-based therapeutic strategies for breast cancer, aiming to provide critical theoretical basis and novel therapeutic perspectives for the clinical translation of CAF heterogeneity research.

摘要

乳腺癌的肿瘤微环境(TME)是一个复杂的生态系统,其中癌症相关成纤维细胞(CAF)作为最丰富的基质细胞类型,精心构建了一个生态位,通过细胞外基质(ECM)重塑、生物活性因子分泌以及与邻近细胞相互作用等机制支持肿瘤生长。包括单细胞测序和空间转录组学在内的高分辨率技术揭示了CAF群体中的高度异质性、功能多样性和空间分布。不同CAF亚群与免疫细胞之间的相互作用存在显著差异。通过与免疫系统的复杂串扰,它们共同建立了一个免疫抑制网络,成为肿瘤免疫逃逸的核心驱动力。本综述聚焦于乳腺癌微环境中CAF异质性亚群的最新研究进展,深入探讨不同CAF亚群与免疫细胞之间复杂的双向串扰如何共同塑造肿瘤免疫微环境(TIME),并总结了基于CAF的各种乳腺癌治疗策略,旨在为CAF异质性研究的临床转化提供关键的理论基础和新颖的治疗视角。

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