Hu Xiaopeng, Li Yanhua, Wang Xisheng, Xue Xingkui
Medical Research Center, People's Hospital of Longhua, Shenzhen, 518000, China.
Department of Pathology, Shenzhen Longhua Maternity and Child Healthcare Hospital, Shenzhen, 518000, China.
Discov Oncol. 2025 May 12;16(1):741. doi: 10.1007/s12672-025-02195-x.
This review summarizes recent findings on the role of M2 tumor-associated macrophages (TAMs) and their exosome-derived non-coding RNAs (ncRNAs) in cancer cell resistance to therapeutics. M2 TAMs promote angiogenesis, suppress immune responses, and facilitate metastasis, thereby creating a tumor-supporting microenvironment. A range of antitumor drugs, including 5-FU, cisplatin, and gemcitabine, are mediated by M2 exosomes, each with distinct mechanisms of action. M2 exosomes transfer drug resistance capabilities via extracellular vesicles, especially exosomes containing miRNAs, lncRNAs, and circRNAs. These exosome mediate the development of tumor drug resistance by regulating signaling pathways such as PI3K/AKT, MAPK/ERK, Wnt/β-catenin M2 exosomes can regulate cellular responses by delivering bioactive molecules, including proteins, lipids, and ncRNA, which can also modulate cellular reactions to ionizing radiation, ultraviolet light, and chemotherapeutic agents. Targeting M2 TAMs and their exosome-mediated ncRNAs may offer new strategies to overcome drug resistance in cancer.
本综述总结了M2肿瘤相关巨噬细胞（TAM）及其外泌体来源的非编码RNA（ncRNA）在癌细胞对治疗的抗性中作用的最新研究结果。M2 TAM促进血管生成、抑制免疫反应并促进转移，从而营造一个支持肿瘤的微环境。一系列抗肿瘤药物，包括5-氟尿嘧啶、顺铂和吉西他滨，均由M2外泌体介导，每种药物都有不同的作用机制。M2外泌体通过细胞外囊泡，特别是含有miRNA、lncRNA和circRNA的外泌体传递耐药能力。这些外泌体通过调节PI3K/AKT、MAPK/ERK、Wnt/β-连环蛋白等信号通路介导肿瘤耐药性的发展。M2外泌体可以通过递送包括蛋白质、脂质和ncRNA在内的生物活性分子来调节细胞反应，这些生物活性分子也可以调节细胞对电离辐射、紫外线和化疗药物的反应。靶向M2 TAM及其外泌体介导的ncRNA可能为克服癌症耐药性提供新策略。
