Tumor-associated macrophages in radiotherapy: Mechanisms of polarization, immune regulation and therapeutic strategies

Macrophages have been shown to play a pivotal role in tumor radiotherapy (RT), particularly in the formation of tumor-associated macrophages (TAMs) in the tumor microenvironment (TME). The number and polarization state of TAMs have been demonstrated to be closely related to the prognosis of tumors. Studies show that the polarization and infiltration of TAMs regulate tumor growth, metastasis and immune escape through multiple mechanisms such as exosomes and cytokines. In RT, TAMs can affect the radiosensitivity of tumors by promoting immunosuppression, angiogenesis and matrix remodeling. However, emerging studies in recent years have demonstrated that TAMs do not always promote tumor progression, and their phenotypes and functions exhibit significant heterogeneity and plasticity, and can even exert anti-tumor effects under certain conditions. A comprehensive understanding of the dynamic changes of TAMs under different RT regimens and their regulatory mechanisms on tumor immune microenvironment (TIME) are crucial for optimizing RT strategies. This review aims to comprehensively illustrate the dual roles of TAMs in tumor radiotherapy and focuses on how to precisely regulate the function and phenotype of TAMs through immunomodulation and targeted therapeutic strategies with the aim of overcoming radioresistance and enhancing tumor radiosensitivity. It is expected to enhance the understanding of the complex relationship between TAMs and RT, and to provide new ideas and a theoretical basis for the development of more effective combined treatment strategies.