Liu Na, Wu Tianqing, Han Guohu, Chen Minbin
Department of Radiotherapy and Oncology, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, China.
XJTLU Wisdom Lake Academy of Pharmacy, Suzhou, Jiangsu Province, China.
Cell Death Discov. 2025 May 6;11(1):221. doi: 10.1038/s41420-025-02484-y.
Ferroptosis in the tumor microenvironment (TME) plays a crucial role in the development, metastasis, immune escape, and drug resistance of various types of cancer. A better understanding of ferroptosis in the TME could illuminate novel aspects of this process and promote the development of targeted therapies. Compelling evidence indicates that exosomes are key mediators in regulating the TME. In this respect, it is now understood that exosomes can deliver biologically functional molecules to recipient cells, influencing cancer progression by reprogramming the metabolism of cancer cells and their surrounding stromal cells through ferroptosis. In this review, we focus on the role of exosomes in the TME and describe how they contribute to tumor reprogramming, immunosuppression, and the formation of pre-metastatic niches through ferroptosis. In addition, we highlight exosome-mediated ferroptosis as a potential target for cancer therapy and discuss strategies employing exosomes in ferroptosis treatment. Finally, we outline the current applications and challenges of targeted exosome-mediated ferroptosis therapy in tumor immunotherapy and chemotherapy. Our aim is to advance research on the link between exosomes and ferroptosis in the TME, and we pose questions to guide future studies in this area.
肿瘤微环境（TME）中的铁死亡在各类癌症的发生、转移、免疫逃逸及耐药性方面发挥着关键作用。深入了解TME中的铁死亡有助于揭示这一过程的新层面，并推动靶向治疗的发展。有力证据表明，外泌体是调节TME的关键介质。在这方面，目前已知外泌体可向受体细胞传递生物功能分子，通过铁死亡对癌细胞及其周围基质细胞的代谢进行重编程，从而影响癌症进展。在本综述中，我们聚焦外泌体在TME中的作用，并描述它们如何通过铁死亡促进肿瘤重编程、免疫抑制及前转移微环境的形成。此外，我们强调外泌体介导的铁死亡作为癌症治疗的潜在靶点，并讨论在外泌体介导的铁死亡治疗中使用外泌体的策略。最后，我们概述了靶向性外泌体介导的铁死亡治疗在肿瘤免疫治疗和化疗中的当前应用及挑战。我们的目的是推动关于TME中外泌体与铁死亡之间联系的研究，并提出问题以指导该领域的未来研究。
