Xia Wenhua, Lv Yuanhao, Zou Yan, Kang Zhanting, Li Zhaoyi, Tian Jiaqi, Zhou Hongyan, Su Wei, Zhong Jiateng
Department of Pathology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China.
Department of Pathology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.
Front Immunol. 2025 Jan 9;15:1526749. doi: 10.3389/fimmu.2024.1526749. eCollection 2024.
Colorectal cancer (CRC) is one of the most prevalent and deadly malignancies worldwide. Recently, ferroptosis, a novel form of regulated cell death characterized by iron dependency and lipid peroxidation, has garnered significant attention from researchers. The mechanisms underlying ferroptosis, including intracellular iron levels, lipid peroxidation, and antioxidant system regulation, offer new insights into cancer treatment strategies. This study aims to explore the emerging role of ferroptosis in the context of immunotherapy for CRC, highlighting its potential mechanisms and clinical applications. We employed a comprehensive review of current literature to elucidate the biological mechanisms of ferroptosis, its relationship with CRC, and the interplay between ferroptosis and immunotherapy. Ferroptosis reshapes the tumor microenvironment (TME) by regulating intracellular iron levels, lipid metabolism, and antioxidant systems, significantly enhancing the efficacy of immune checkpoint inhibitors (ICIs). Meanwhile, traditional Chinese medicine therapies promote antitumor immunity by modulating the TME and inducing ferroptosis. Additionally, advances in nanotechnology have facilitated precise therapy by enabling targeted delivery of ferroptosis inducers or immunomodulators, transforming "cold" tumors into "hot" tumors and further boosting ICI efficacy. This study comprehensively reviews the latest developments in ferroptosis, immunotherapy, traditional Chinese medicine, and nanotechnology in CRC, highlighting the importance of ferroptosis-related biomarkers and novel inducers for personalized treatment. In summary, ferroptosis offers a promising strategy to overcome CRC therapy resistance and enhance immunotherapy efficacy, warranting further investigation and translational application.
结直肠癌（CRC）是全球最常见且致命的恶性肿瘤之一。最近，铁死亡作为一种新型的程序性细胞死亡形式，其特征为铁依赖性和脂质过氧化，已引起研究人员的广泛关注。铁死亡的潜在机制，包括细胞内铁水平、脂质过氧化和抗氧化系统调节，为癌症治疗策略提供了新的见解。本研究旨在探讨铁死亡在CRC免疫治疗背景下的新作用，突出其潜在机制和临床应用。我们通过对当前文献进行全面综述，以阐明铁死亡的生物学机制、其与CRC的关系以及铁死亡与免疫治疗之间的相互作用。铁死亡通过调节细胞内铁水平、脂质代谢和抗氧化系统重塑肿瘤微环境（TME），显著增强免疫检查点抑制剂（ICI）的疗效。同时，中药疗法通过调节TME和诱导铁死亡来促进抗肿瘤免疫。此外，纳米技术的进步通过实现铁死亡诱导剂或免疫调节剂的靶向递送促进了精准治疗，将“冷”肿瘤转化为“热”肿瘤并进一步提高ICI疗效。本研究全面综述了CRC中铁死亡、免疫治疗、中药和纳米技术的最新进展，强调了铁死亡相关生物标志物和新型诱导剂在个性化治疗中的重要性。总之，铁死亡为克服CRC治疗耐药性和提高免疫治疗疗效提供了一种有前景的策略，值得进一步研究和转化应用。
