Xia Cong, Luo Zirun, Feng Zhen, Zhang Qianshi, Xia Chenglai
Department of Gastrointestinal Surgery, The Second Hospital of Dalian Medical University, Dalian, China.
Department of Breast, Thyroid and Head-Neck Surgery, The Third Xiangya Hospital of Central South University, Changsha, China.
Front Pharmacol. 2025 Jul 11;16:1646890. doi: 10.3389/fphar.2025.1646890. eCollection 2025.
Immunotherapy stands as a powerful weapon against tumors. However, tumor cells evade recognition and attack by the immune system through various mechanisms, achieving immune escape and exhibiting resistance to immunotherapy. Metalloimmunotherapy, as an emerging paradigm for immunotherapy, offers the potential to effectively overcome the limitations of current tumor immunotherapies. Nevertheless, developing highly efficient and specific metal-based agents for regulating the tumor immune system remains a significant challenge. The modulation of oxidative stress in the tumor microenvironment (TME) by metals presents novel breakthroughs for metalloimmunotherapy, particularly in enhancing immune responses, optimizing immune cell function, and reprogramming the immunosuppressive TME. Copper, a transition metal closely associated with tumor development, acts as an immune activator to enhance immune responses through oxidative stress. Benefiting from advances in nanomaterials, copper-based nanomedicines have demonstrated significant potential in improving the efficacy of cancer immunotherapy by modulating oxidative stress via Fenton-like reactions and enzymatic catalytic activities. Therefore, summarizing recent advances in copper-based nanomedicine activating tumor immunity through oxidative stress modulation provides new insights and drives progress for metalloimmunology. This review outlines strategies utilizing oxidative stress modulated by copper-based nanomedicines to induce or enhance immunotherapy through multiple forms of regulated cell death (RCD), drug co-delivery approaches, and versatile combination therapies. Finally, we discuss current challenges and offer perspectives on copper-based nanomedicines in tumor immunotherapy. Our review aims to elucidate the potential of copper-based nanomedicines in tumor immunology, providing insights for the future development of tumor immunotherapies based on metal and redox biology.
免疫疗法是对抗肿瘤的有力武器。然而,肿瘤细胞通过各种机制逃避免疫系统的识别和攻击,实现免疫逃逸并表现出对免疫疗法的抗性。金属免疫疗法作为一种新兴的免疫疗法范式,有望有效克服当前肿瘤免疫疗法的局限性。尽管如此,开发高效、特异性的金属基制剂来调节肿瘤免疫系统仍然是一项重大挑战。金属对肿瘤微环境(TME)中氧化应激的调节为金属免疫疗法带来了新的突破,特别是在增强免疫反应、优化免疫细胞功能和重编程免疫抑制性TME方面。铜作为一种与肿瘤发展密切相关的过渡金属,通过氧化应激充当免疫激活剂来增强免疫反应。受益于纳米材料的进展,铜基纳米药物通过类芬顿反应和酶催化活性调节氧化应激,在提高癌症免疫疗法疗效方面已显示出巨大潜力。因此,总结铜基纳米药物通过氧化应激调节激活肿瘤免疫的最新进展,为金属免疫学提供了新的见解并推动其发展。本综述概述了利用铜基纳米药物调节氧化应激,通过多种形式的调节性细胞死亡(RCD)、药物共递送方法和多功能联合疗法诱导或增强免疫疗法的策略。最后,我们讨论了当前的挑战,并对铜基纳米药物在肿瘤免疫疗法中的应用提出了展望。我们的综述旨在阐明铜基纳米药物在肿瘤免疫学中的潜力,为基于金属和氧化还原生物学的肿瘤免疫疗法的未来发展提供见解。
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