Bu Xiaorui, Wang Lufang
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
Int J Mol Med. 2025 Mar;55(3). doi: 10.3892/ijmm.2024.5480. Epub 2025 Jan 3.
Iron metabolism plays a crucial role in the tumor microenvironment, influencing various aspects of cancer cell biology and tumor progression. This review discusses the regulatory mechanisms of iron metabolism within the tumor microenvironment and highlights how tumor cells and associated stromal cells manage iron uptake, accumulation and regulation. The sources of iron within tumors and the biological importance of ferroptosis in cancer were explored, focusing on its mechanisms, biological effects and, in particular, its tumor‑suppressive properties. Furthermore, the protective strategies employed by cancer cells to evade ferroptosis were examined. This review also delves into the intricate relationship between iron metabolism and immune modulation within the tumor microenvironment, detailing the impact on tumor‑associated immune cells and immune evasion. The interplay between ferroptosis and immunotherapy is discussed and potential strategies to enhance cancer immunotherapy by modulating iron metabolism are presented. Finally, the current ferroptosis‑based cancer therapeutic approaches were summarized and future directions for therapies that target iron metabolism were proposed.
铁代谢在肿瘤微环境中起着关键作用,影响癌细胞生物学和肿瘤进展的各个方面。本综述讨论了肿瘤微环境中铁代谢的调节机制,并强调了肿瘤细胞和相关基质细胞如何管理铁的摄取、积累和调节。探讨了肿瘤内铁的来源以及铁死亡在癌症中的生物学重要性,重点关注其机制、生物学效应,特别是其肿瘤抑制特性。此外,还研究了癌细胞用于逃避铁死亡的保护策略。本综述还深入探讨了肿瘤微环境中铁代谢与免疫调节之间的复杂关系,详细阐述了对肿瘤相关免疫细胞和免疫逃逸的影响。讨论了铁死亡与免疫治疗之间的相互作用,并提出了通过调节铁代谢增强癌症免疫治疗的潜在策略。最后,总结了当前基于铁死亡的癌症治疗方法,并提出了针对铁代谢的治疗未来方向。