Macrophage-cancer cell crosstalk in breast cancer chemotherapy resistance

Breast cancer (BC) represents one of the most prevalent malignancies in the female population and constitutes a leading cause of cancer-associated mortality among women globally. The emergence of chemoresistance persists as a critical challenge in current breast cancer therapeutic strategies. Malignant tumors are enveloped by a sophisticated assemblage of cellular and non-cellular components that collectively establish the tumor microenvironment (TME). Notably, tumor-associated macrophages (TAMs), being one of the most abundant immune infiltrates within the TME, have been demonstrated to play an instrumental role in the development and progression of chemotherapeutic resistance mechanisms. Recent studies have revealed that TAMs and breast cancer cells engage in complex bidirectional interactions. This crosstalk not only facilitates tumor immune evasion but also promotes chemotherapy resistance in breast cancer through the secretion of various cytokines, chemokines, growth factors, and other bioactive molecules. Therefore, elucidating the underlying mechanisms by which TAMs contribute to chemotherapy resistance is of significant importance. This review summarizes the dynamic and bidirectional regulatory network formed between TAMs and BC. Centering on this network, it comprehensively analyzes the molecular mechanisms by which TAMs regulate chemotherapy resistance in BC, summarizes potential targeted drugs that disrupt molecular interactions between TAMs and BC, and discusses the therapeutic prospects of combining these drugs with chemotherapy and immunotherapy. The findings aim to provide novel insights into potential molecular targets for overcoming chemotherapy resistance and to explore new therapeutic strategies for breast cancer patients.