Wang Yi, Tang Chuanyun, Wang Keqin, Zhang Xiaoan, Zhang Lifang, Xiao Xinghua, Lin Hui, Xiong Lixia
The MOE Basic Research and Innovation Center for the Targeted Therapeutics of Solid Tumors, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang, 330006, China.
First Clinical Medical College, Nanchang University, Nanchang, 330006, China.
Eur J Pharmacol. 2025 Jun 5;996:177561. doi: 10.1016/j.ejphar.2025.177561. Epub 2025 Mar 26.
Ferroptosis represents a distinctive and distinct form of regulated cellular death, which is driven by the accumulation of lipid peroxidation. It is distinguished by altered redox lipid metabolism and is linked to a spectrum of cellular activities, including cancer. In breast cancer (BC), with triple negative breast cancer (TNBC) being an iron-and lipid-rich tumor, inducing ferroptosis was thought to be a novel approach to killing breast tumor cells. However, in the recent past, a novel conceptual framework has emerged which posits that in addition to the promotion of tumor cell death, ferritin deposition has a potent immunosuppressive effect on the tumor immune microenvironment (TIME) via the influence on both innate and adaptive immune responses. TIME of BC includes various cell populations from both the innate and adaptive immune systems. In this review, the internal association between iron homeostasis and the progression of ferroptosis, along with the common inducers and protectors of ferroptosis in BC, are discussed in detail. Furthermore, a comprehensive analysis is conducted on the dual role of ferroptosis in immune cells and proto-oncogenic functions, along with an evaluation of the potential applications of immunogenic cell death-targeted immunotherapy in TIME of BC. It is anticipated that our review will inform future research endeavors that seek to integrate ferroptosis and immunotherapy in the management of BC.
铁死亡是一种独特且受调控的细胞死亡形式，由脂质过氧化的积累所驱动。它以氧化还原脂质代谢的改变为特征，并与一系列细胞活动相关，包括癌症。在乳腺癌（BC）中，三阴性乳腺癌（TNBC）是一种富含铁和脂质的肿瘤，诱导铁死亡被认为是杀死乳腺肿瘤细胞的一种新方法。然而，最近出现了一个新的概念框架，该框架认为，除了促进肿瘤细胞死亡外，铁蛋白沉积还通过影响先天性和适应性免疫反应，对肿瘤免疫微环境（TIME）具有强大的免疫抑制作用。BC的TIME包括来自先天性和适应性免疫系统的各种细胞群体。在本综述中，详细讨论了铁稳态与铁死亡进展之间的内在联系，以及BC中铁死亡的常见诱导剂和保护剂。此外，还对铁死亡在免疫细胞和原癌功能中的双重作用进行了全面分析，并评估了靶向免疫原性细胞死亡的免疫疗法在BC的TIME中的潜在应用。预计我们的综述将为未来旨在将铁死亡和免疫疗法整合到BC治疗中的研究努力提供参考。
