Hu Lihong, Hu Jiejie, Qin Chengdong, Liu Siyuan, Yu Yang
Postgraduate Training Base Alliance of Wenzhou Medical University, Zhejiang Cancer Hospital), Hangzhou, Zhejiang, China.
Department of Breast Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China.
Mol Cell Biochem. 2025 May 29. doi: 10.1007/s11010-025-05305-z.
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited treatment options and a poor prognosis. Immunotherapy has emerged as a promising approach for TNBC, with tumor-infiltrating immune cells (TICs) in the tumor microenvironment (TME) serving as a critical cellular basis for its efficacy. However, the success of immunotherapy in TNBC is often limited due to the immunosuppressive nature of the TME and the heterogeneity of TNBC. Ferroptosis, a form of iron-dependent programmed cell death regulated by metabolic networks including iron, glutathione (GSH), and lipid metabolism, has shown potential to enhance anti-tumor immunity. Recent studies have demonstrated that ferroptosis can modulate immune responses by promoting the infiltration and activation of TICs, thereby improving the outcomes of immunotherapy. However, ferroptosis in immunosuppressive cells such as regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) can trigger an "immunosuppressive wave," affecting other immune cells in the tumor immune microenvironment. This demonstrates the dual role of ferroptosis in TNBC therapy, emphasizing the need for a nuanced understanding of its effects on different immune cells and tumor cells. Herein, we further elaborate the role of ferroptosis in TNBC cells and its interactions with tumor-infiltrating immune cells (TICs) within the TME.
三阴性乳腺癌（TNBC）是一种侵袭性乳腺癌亚型，治疗选择有限且预后较差。免疫疗法已成为TNBC一种有前景的治疗方法，肿瘤微环境（TME）中的肿瘤浸润免疫细胞（TICs）是其疗效的关键细胞基础。然而，由于TME的免疫抑制性质和TNBC的异质性，免疫疗法在TNBC中的成功往往受到限制。铁死亡是一种由包括铁、谷胱甘肽（GSH）和脂质代谢在内的代谢网络调节的铁依赖性程序性细胞死亡形式，已显示出增强抗肿瘤免疫力的潜力。最近的研究表明，铁死亡可通过促进TICs的浸润和激活来调节免疫反应，从而改善免疫治疗的效果。然而，调节性T细胞（Tregs）和髓源性抑制细胞（MDSCs）等免疫抑制细胞中的铁死亡可引发“免疫抑制波”，影响肿瘤免疫微环境中的其他免疫细胞。这证明了铁死亡在TNBC治疗中的双重作用，强调需要细致了解其对不同免疫细胞和肿瘤细胞的影响。在此，我们进一步阐述铁死亡在TNBC细胞中的作用及其与TME内肿瘤浸润免疫细胞（TICs）的相互作用。
