CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Nanozyme-Mediated Cellular and Microenvironmental Metabolic Reprogramming for Boosting Cancer Immunotherapy.
Nanozyme-Mediated Cellular and Microenvironmental Metabolic Reprogramming for Boosting Cancer Immunotherapy.
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癌症免疫疗法的有效性常因高度免疫抑制的肿瘤微环境(TME)而受损,该微环境的特征在于促肿瘤代谢异常,包括缺氧、营养竞争以及毒性代谢物的积累。在此,我们综述了纳米酶通过直接调控免疫代谢通路来增强免疫治疗疗效的潜力。我们描述了具有不同催化特性的纳米酶如何重编程TME以缓解缺氧、补充营养并清除免疫抑制性代谢物如谷胱甘肽和犬尿氨酸。纳米酶驱动的肿瘤免疫代谢景观的生物催化重塑增强了抗原呈递细胞(APCs)的功能和成熟,同时阻断免疫抑制细胞如调节性T细胞(Tregs)和髓源性抑制细胞(MDSCs),从而恢复抗肿瘤T细胞的代谢适应性。此外,我们探讨了纳米酶与现有免疫治疗药物如免疫检查点抑制剂(ICB)、过继细胞疗法和癌症疫苗的协同作用。最后,我们讨论了将这些发现转化为临床实践的挑战,并提出了将这些基于纳米酶的策略整合到创新联合疗法中的未来方向。
The effectiveness of cancer immunotherapy is often compromised by a highly immunosuppressive tumor microenvironment (TME), characterized by pro-tumorigenic metabolic abnormalities including hypoxia, nutrient competition, and accumulation of toxic metabolites.
Here, we review the potential of nanozymes to directly modulate immunometabolic pathways to empower immunotherapeutic efficacy.
We describe how nanozymes with distinct catalytic properties can reprogram the TME to alleviate hypoxia, supplement nutrients, and eliminate immunosuppressive metabolites such as glutathione and kynurenine. The nanozyme-enabled biocatalytic remodeling of tumor immunometabolic landscape enhances the function and maturation of antigen-presenting cells (APCs) while blocking immunosuppressive cells such as regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), leading to the restoration of metabolic fitness of antitumorigenic T cells.
Furthermore, we explore the synergy of nanozymes with established immunotherapeutics such as immune checkpoint inhibitors (ICB), adoptive cell therapies, and cancer vaccines.
Finally, we address the challenges of translating these findings into clinical practice and propose future directions for integrating these nanozyme-based strategies into innovative combination therapies.
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