Role of Biological Mediators of Tumor-Associated Macrophages in Breast Cancer Progression

Background: Breast cancer (BRCA) has become the most common cancer worldwide. The tumor microenvironment (TME) in the breast exerts a crucial role in promoting BRCA initiation, progression, and metastasis. Tumor-associated macrophages (TAMs) are the primary component of tumor-infiltrating immune cells through biological mediators that convert TME into malignant tumors. Combinations of these biological mediators can promote tumor growth, metastasis, angiogenesis, and immune suppression and limit the anti-tumor activity of conventional chemotherapy and radiotherapy. Objectives: The present study aimed to highlight the functions of several biological mediators in the breast thatgenerate TME into malignant tumors. Furthermore, this review offers a rationale for TAM-targeted therapy as a novel treatment strategy for BRCA. Results: This review emphasizes TAM-associated biological mediators of TME, viz., cancer-associated fibroblasts, endothelial cells, adipocytes, tumor-derived exosomes, extracellular matrix, and other immune cells, which facilitate TME in malignant tumors. Evidence suggests that the increased infiltration of TAMs and elevated expression of TAM-related genes are associated with a poor prognosis of BRCA. Based on these findings, TAM-targeted therapeutic strategies, including inhibitors of CSF-1/CSF-1R, CCL2/CCR2, CCL5-CCR5, bisphosphonate, nanoparticle, and exosomal-targeted delivery have been developed, and are currently being employed in intervention trials. Conclusion: This review concludes the roles of biological mediators of TME that interact with TAMs in BRCA, providing a rationale for TAM-targeted therapy as a novel treatment approach for BRCA.

Automated summary

This review highlights the biological mediators associated with tumor-associated macrophages (TAMs) in the tumor microenvironment (TME) of breast cancer (BRCA), including cancer-associated fibroblasts, endothelial cells, adipocytes, tumor-derived exosomes, extracellular matrix, and other immune cells. Increased infiltration of TAMs and elevated expression of TAM-related genes have been linked to a poor prognosis of BRCA. TAM-targeted therapeutic strategies, such as inhibitors of CSF-1/CSF-1R, CCL2/CCR2, CCL5-CCR5, bisphosphonate, nanoparticle, and exosomal-targeted delivery, have been developed and are currently being tested in intervention trials.