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

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.