Liu Long, Zhang Siying, Ren Yuqing, Wang Ruizhi, Zhang Yuyuan, Weng Siyuan, Zhou Zhaokai, Luo Peng, Cheng Quan, Xu Hui, Ba Yuhao, Zuo Anning, Liu Shutong, Liu Zaoqu, Han Xinwei
Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
J Nanobiotechnology. 2025 Apr 26;23(1):319. doi: 10.1186/s12951-025-03321-1.
Solid cancer contains a complicated communication network between cancer cells and components in the tumor microenvironment (TME), significantly influencing the progression of cancer. Exosomes function as key carriers of signaling molecules in these communications, including the intricate signalings of tumor-associated macrophages (TAMs) on cancer cells and the TME. With their natural lipid bilayer structures and biological activity that relates to their original cell, exosomes have emerged as efficient carriers in studies on cancer therapy. Intrigued by the heterogeneity and plasticity of both macrophages and exosomes, we regard macrophage-derived exosomes in cancer as a double-edged sword. For instance, TAM-derived exosomes, educated by the TME, can promote resistance to cancer therapies, while macrophage-derived exosomes generated in vitro have shown favorable potential in cancer therapy. Here, we depict the reasons for the heterogeneity of TAM-derived exosomes, as well as the manifold roles of TAM-derived exosomes in cancer progression, metastasis, and resistance to cancer therapy. In particular, we emphasize the recent advancements of modified macrophage-derived exosomes in diverse cancer therapies, arguing that these modified exosomes are endowed with unique advantages by their macrophage origin. We outline the challenges in translating these scientific discoveries into clinical cancer therapy, aiming to provide patients with safe and effective treatments.
实体癌在癌细胞与肿瘤微环境（TME）中的成分之间包含一个复杂的通讯网络，对癌症进展有显著影响。外泌体在这些通讯中作为信号分子的关键载体，包括肿瘤相关巨噬细胞（TAM）对癌细胞和TME的复杂信号传导。凭借其天然的脂质双层结构以及与原始细胞相关的生物活性，外泌体已成为癌症治疗研究中的有效载体。受巨噬细胞和外泌体的异质性和可塑性的启发，我们认为癌症中巨噬细胞衍生的外泌体是一把双刃剑。例如，由TME塑造的TAM衍生的外泌体可促进对癌症治疗的抗性，而体外产生的巨噬细胞衍生的外泌体在癌症治疗中已显示出良好的潜力。在此，我们描述了TAM衍生的外泌体异质性的原因，以及TAM衍生的外泌体在癌症进展、转移和对癌症治疗的抗性中的多种作用。特别是，我们强调了修饰的巨噬细胞衍生的外泌体在多种癌症治疗中的最新进展，认为这些修饰的外泌体因其巨噬细胞来源而具有独特优势。我们概述了将这些科学发现转化为临床癌症治疗所面临的挑战，旨在为患者提供安全有效的治疗方法。
