State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, 610041 Chengdu, Sichuan, China.
Department of Stomatology, Panzhihua Central Hospital, 617000 Panzhihua, Sichuan, China.
Front Biosci (Landmark Ed). 2022 Jun 27;27(7):203. doi: 10.31083/j.fbl2707203.
Ferroptosis is an emerging form of non-apoptotic, regulated cell death that is mechanistically dependent on aberrant iron accumulation and excessive lipid peroxidation. Further evidence indicates that ferroptosis plays a crucial role in the efficacy of tumor immunotherapy. Ferroptosis is often constrained by tumor-associated macrophages (TAMs), and this poses a challenge to clinicians aiming to exploit the potency of immunotherapy to treat various forms of cancer. Current advances revealed a dual character to TAMs in regulating tumor ferroptosis. Specifically, some signaling molecules released from cells undergoing ferroptosis can exert effects on TAM polarization. In this review, we summarize the currently characterized mechanisms of macrophage-ferroptosis crosstalk, discuss how macrophage-ferroptosis crosstalk affects the outcome of tumor immunotherapy, and provide an overview of current advances that seek to leverage this crosstalk to improve cancer immunotherapy efficacy. Despite the fact that further efforts are still required to achieve a more comprehensive understanding of the mechanisms that control this signaling, targeting macrophage-ferroptosis crosstalk has clear potential for reversing immunotherapeutic resistance and may shed light on new therapeutic strategies to overcome some advanced and metastatic malignancies.
铁死亡是一种新兴的非凋亡性、受调控的细胞死亡形式，其机制上依赖于异常的铁积累和过度的脂质过氧化。进一步的证据表明，铁死亡在肿瘤免疫治疗的疗效中起着至关重要的作用。铁死亡通常受到肿瘤相关巨噬细胞（TAMs）的限制，这给旨在利用免疫疗法治疗各种形式癌症的临床医生带来了挑战。目前的进展揭示了 TAMs 在调节肿瘤铁死亡方面的双重特征。具体来说，细胞发生铁死亡时释放的一些信号分子可以对 TAM 极化产生影响。在这篇综述中，我们总结了目前表征的巨噬细胞-铁死亡相互作用的机制，讨论了巨噬细胞-铁死亡相互作用如何影响肿瘤免疫治疗的结果，并概述了目前寻求利用这种相互作用来提高癌症免疫治疗疗效的进展。尽管为了更全面地了解控制这种信号的机制还需要进一步努力，但靶向巨噬细胞-铁死亡相互作用具有逆转免疫治疗耐药性的明确潜力，并可能为克服一些晚期和转移性恶性肿瘤提供新的治疗策略。
