Cancer Center, the First Hospital of Jilin University, Changchun, Jilin 130021, China.
Cancer Center, the First Hospital of Jilin University, Changchun, Jilin 130021, China.
Biomed Pharmacother. 2024 Oct;179:117298. doi: 10.1016/j.biopha.2024.117298. Epub 2024 Aug 15.
Immune checkpoint blocking (ICB), a tumor treatment based on the mechanism of T-cell activation, has shown high efficacy in clinical trials, but not all patients benefit from it. Immune checkpoint inhibitors (ICIs) do not respond to cold tumors that lack effective T-cell infiltration but respond well to hot tumors with sufficient T-cell infiltration. How to convert an unresponsive cold tumor into a responsive hot tumor is an important topic in cancer immunotherapy. Ferroptosis, a newly discovered immunogenic cell death (ICD) form, has great potential in cancer therapy. In the process of deeply understanding the mechanism of cold tumor formation, it was found that ferroptosis showed a powerful immune-activating effect by improving T-cell infiltration, and the combination of ICB therapy significantly enhanced the anti-tumor efficacy. This paper reviews the complex relationship between T cells and ferroptosis, as well as summarizes the various mechanisms by which ferroptosis enhances T cell infiltration: reactivation of T cells and reversal of immunosuppressive tumor microenvironment (TME), as well as recent advances of ICI in combination with targeted ferroptosis therapies, which provides guidance for better improving the ICB efficacy of cold tumors.
免疫检查点阻断（ICB）是一种基于 T 细胞激活机制的肿瘤治疗方法，在临床试验中显示出了很高的疗效，但并非所有患者都从中受益。免疫检查点抑制剂（ICIs）对缺乏有效 T 细胞浸润的冷肿瘤没有反应，但对 T 细胞浸润充足的热肿瘤反应良好。如何将无反应的冷肿瘤转化为有反应的热肿瘤是癌症免疫治疗的一个重要课题。铁死亡是一种新发现的免疫原性细胞死亡（ICD）形式，在癌症治疗中有很大的潜力。在深入了解冷肿瘤形成机制的过程中，人们发现铁死亡通过改善 T 细胞浸润表现出强大的免疫激活作用，并且 ICB 治疗的联合显著增强了抗肿瘤疗效。本文综述了 T 细胞与铁死亡之间的复杂关系，并总结了铁死亡增强 T 细胞浸润的多种机制：T 细胞的再激活和逆转免疫抑制性肿瘤微环境（TME），以及最近 ICI 与靶向铁死亡治疗联合的进展，为更好地提高冷肿瘤的 ICB 疗效提供了指导。
