Focusing on the interplay between tumor-associated macrophages and tumor microenvironment: from mechanism to intervention

Immunotherapy has generated promising outcomes in cancer treatment; however, therapeutic responses are hampered by immunosuppression in the tumor microenvironment (TME). This has resulted in increased study of key immune cells in the TME as therapeutic interventions. Tumor-associated macrophages (TAMs), a major component of infiltrating immune cells in the TME, display high plasticity, largely dependent on cues received from their surroundings. Although significant progress in metabolomics and single-cell omics has unraveled the metabolic and functional heterogeneity of TAMs across several types of cancer, the development of TAM-targeted therapy remains challenging. In the present review, the crosstalk between TAMs and other components in TME, such as tumor cells, immune cells, cancer-associated fibroblasts, and extracellular matrix is highlighted. Additionally, updated insights into the origin, heterogeneity, and metabolic reprogramming of TAMs are discussed, and relevant approaches of targeting TAMs in clinical investigations are summarized. The present review provides a deeper understanding of TAMs within the microenvironment network, aimed at identifying candidate targets to improve cancer immunotherapy.