放射治疗中的肿瘤相关巨噬细胞:极化机制、免疫调节及治疗策略
Tumor-associated macrophages in radiotherapy: Mechanisms of polarization, immune regulation and therapeutic strategies.
作者信息
Xu Junguang, Mo Jintao, Jiang Yihan, Yang Tianpeng, Lu Zipeng, Han Liu, Ding Jinyan, Shi Fang, Liu Rui
机构信息
School of Public Health, Wenzhou Medical University, Wenzhou 325035, China.
School of the First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou 325035, China.
出版信息
Int Immunopharmacol. 2025 Aug 28;161:115009. doi: 10.1016/j.intimp.2025.115009. Epub 2025 Jun 5.
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.
巨噬细胞已被证明在肿瘤放疗(RT)中起关键作用,尤其是在肿瘤微环境(TME)中肿瘤相关巨噬细胞(TAM)的形成方面。TAM的数量和极化状态已被证明与肿瘤预后密切相关。研究表明,TAM的极化和浸润通过外泌体和细胞因子等多种机制调节肿瘤生长、转移和免疫逃逸。在放疗中,TAM可通过促进免疫抑制、血管生成和基质重塑来影响肿瘤的放射敏感性。然而,近年来的新研究表明,TAM并不总是促进肿瘤进展,其表型和功能表现出显著的异质性和可塑性,甚至在某些条件下可发挥抗肿瘤作用。全面了解不同放疗方案下TAM的动态变化及其对肿瘤免疫微环境(TIME)的调控机制,对于优化放疗策略至关重要。本综述旨在全面阐述TAM在肿瘤放疗中的双重作用,并重点关注如何通过免疫调节和靶向治疗策略精确调控TAM的功能和表型,以克服放射抗性并提高肿瘤放射敏感性。期望增进对TAM与放疗之间复杂关系的理解,并为开发更有效的联合治疗策略提供新思路和理论依据。