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肿瘤微环境中 MDSCs 的代谢重编程及其在癌症免疫治疗中的靶向作用。

Metabolic reprograming of MDSCs within tumor microenvironment and targeting for cancer immunotherapy.

机构信息

Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430000, China.

出版信息

Acta Pharmacol Sin. 2022 Jun;43(6):1337-1348. doi: 10.1038/s41401-021-00776-4. Epub 2021 Sep 24.

Abstract

A number of emerging studies in field of immune metabolism have indicated that cellular metabolic reprograming serves as a major administrator in maintaining the viability and functions of both tumor cells and immune cells. As one of the most important immunosuppressive cells in tumor stroma, myeloid-derived suppressor cells (MDSCs) dynamically orchestrate their metabolic pathways in response to the complicated tumor microenvironment (TME), a process that consequently limits the therapeutic effectiveness of anti-cancer treatment modalities. In this context, the metabolic vulnerabilities of MDSCs could be exploited as a novel immune metabolic checkpoint upon which to intervene for promoting the efficacy of immunotherapy. Here, we have discussed about recent studies highlighting the important roles of the metabolic reprograming and the core molecular pathways involved in tumor-infiltrating MDSCs. In addition, we have also summarized the state-of-the-art strategies that are currently being employed to target MDSC metabolism and improve the efficacy of antineoplastic immunotherapy.

摘要

许多新兴的免疫代谢研究表明,细胞代谢重编程是维持肿瘤细胞和免疫细胞活力和功能的主要调控者。髓系来源的抑制细胞(MDSCs)作为肿瘤基质中最重要的免疫抑制细胞之一,能够根据复杂的肿瘤微环境(TME)动态协调其代谢途径,从而限制了抗肿瘤治疗方式的疗效。在这种情况下,MDSCs 的代谢脆弱性可以作为一种新的免疫代谢检查点加以利用,以促进免疫治疗的效果。在这里,我们讨论了最近的研究,强调了代谢重编程以及肿瘤浸润性 MDSCs 中涉及的核心分子途径的重要作用。此外,我们还总结了目前用于靶向 MDSC 代谢和提高抗肿瘤免疫治疗效果的最新策略。

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