Dual roles of GM-CSF in breast cancer: Immunomodulation and therapeutic implications

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic growth factor secreted by immune and non-immune cells. By binding to specific receptors on target cell surfaces, GM-CSF promotes hematopoiesis, activates immune cells, modulates inflammatory responses, participates in tissue repair, and regulating anti-tumor immunity. Breast cancer is the most prevalent malignancy among women worldwide and the leading cause of cancer-related mortality in females. The pathogenesis of breast cancer is complex, with the tumor microenvironment (TME) playing a pivotal role in disease initiation and progression. The TME comprises malignant tumor cells, immune cells, and stromal cells, where oncogenic mutations in malignant cells drive carcinogenesis and reprogram the functionality of surrounding non-malignant cells through intercellular communication molecules, such as cytokines, chemokines, and extracellular vesicles, thereby promoting or suppressing tumor progression. Beyond its direct effects on tumor cells, GM-CSF exhibits dual roles in the TME: On one hand, it exerts anti-tumor immune effects by activating immune cells, enhancing antigen presentation capacity, and improving tumor vaccine efficacy; on the other hand, it may promote the activation of tumor-associated macrophages, tumor-associated neutrophils, and myeloid-derived suppressor cells, thereby suppressing immune responses and facilitating tumor growth and metastasis. This review systematically summarizes the regulatory roles of GM-CSF in breast cancer progression based on its structure and biological functions, and explores its therapeutic potential through various strategies including vaccine development, combination therapies, and nanoparticle-based delivery systems. These insights may provide novel perspectives for future mechanistic investigations and clinical applications of GM-CSF.