Role of Tumor-Associated Macrophages in Breast Cancer Immunotherapy.

Breast cancer (BC) is the second leading cause of death among women worldwide. Immunotherapy has become an effective treatment for BC patients due to the rapid development of medical technology. Considerable breakthroughs have been made in research, marking the beginning of a new era in cancer treatment. Among them, various cancer immunotherapies such as immune checkpoint inhibitors (ICIs), cancer vaccines, and adoptive cell transfer are effective and have good prospects. The tumor microenvironment (TME) plays a crucial role in determining the outcomes of tumor immunotherapy. Tumor-associated macrophages (TAMs) are a key component of the TME, with an immunomodulatory effect closely related to the immune evasion of tumor cells, thereby affecting malignant progression. TAMs also significantly affect the therapeutic effect of ICIs (such as programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors). TAMs are composed of multiple heterogeneous subpopulations, including M1 phenotypes macrophages (M1) and M2 phenotypes macrophages (M2). Furthermore, they mainly play an M2-like role and moderate a variety of harmful consequences such as angiogenesis, immunosuppression, and metastasis. Therefore, TAMs have become a key area of focus in the development of tumor therapies. However, several tumor immunotherapy studies demonstrated that ICIs are effective only in a small number of solid cancers, and tumor immunotherapy still faces relevant challenges in the treatment of solid tumors. This review explores the role of TAMs in BC immunotherapy, summarizing their involvement in BC development. It also explains the classification and functions of TAMs, outlines current tumor immunotherapy approaches and combination therapies, and discusses the challenges and potential strategies for TAMs in immuno-oncology treatments.