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

Yuxuan Guo; Yingya Hu; Da Huang; Jiangnan Yang; Shujun Fu; Xiyun Deng; Jun Long; Jie Wang; Yian Wang

doi:10.1016/j.critrevonc.2025.104804

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

Crit Rev Oncol Hematol. 2025 Jun 16:214:104804. doi: 10.1016/j.critrevonc.2025.104804. Online ahead of print.

Authors

Yuxuan Guo¹, Yingya Hu¹, Da Huang², Jiangnan Yang¹, Shujun Fu¹, Xiyun Deng¹, Jun Long³, Jie Wang⁴, Yian Wang⁵

Affiliations

¹ Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, Hunan Normal University Health Science Center, Changsha 410013, China; Engineering Research Center of Reproduction and Translational Medicine of Hunan Province, Changsha 410013, China.
² The Fourth Hospital of Changsha(Integrated Traditional Chinese and Western Medicine Hospital of Changsha, Changsha Hospital of Hunan Normal University), Changsha 410013, China.
³ Shenzhen Key Laboratory of Energy Electrocatalytic Materials, Shenzhen Key Laboratory of Polymer Science and Technology, Guangdong Provincial Key Laboratory of New Energy Materials Service Safety, College of Materials Science and Engineering, Shenzhen University, Shenzhen 518060, China.
⁴ Department of Pathology, Institute of Oncology & Diagnostic Pathology Center, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China. Electronic address: helenajiewang@fjmu.edu.cn.
⁵ Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, Hunan Normal University Health Science Center, Changsha 410013, China; Engineering Research Center of Reproduction and Translational Medicine of Hunan Province, Changsha 410013, China. Electronic address: wangyian@hunnu.edu.cn.

PMID: 40516637
DOI: 10.1016/j.critrevonc.2025.104804

Abstract

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.

Keywords: Breast cancer; Dual role; Granulocyte-macrophage colony-stimulating factor; Immunotherapy; Tumor microenvironment.

Publication types

Review