Lu Junli, Luo Yiming, Rao Dean, Wang Tiantian, Lei Zhen, Chen Xiaoping, Zhang Bixiang, Li Yiwei, Liu Bifeng, Xia Limin, Huang Wenjie
Hepatic Surgery Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Wuhan, 430030, Hubei, China.
Clinical Medicine Research Center for Hepatic Surgery of Hubei Province, Key Laboratory of Organ Transplantation, Ministry of Education and Ministry of Public Health, Wuhan, 430030, Hubei, China.
Exp Hematol Oncol. 2024 Apr 12;13(1):39. doi: 10.1186/s40164-024-00505-7.
Paradoxically, tumor development and progression can be inhibited and promoted by the immune system. After three stages of immune editing, namely, elimination, homeostasis and escape, tumor cells are no longer restricted by immune surveillance and thus develop into clinical tumors. The mechanisms of immune escape include abnormalities in antitumor-associated immune cells, selection for immune resistance to tumor cells, impaired transport of T cells, and the formation of an immunosuppressive tumor microenvironment. A population of distinct immature myeloid cells, myeloid-derived suppressor cells (MDSCs), mediate immune escape primarily by exerting immunosuppressive effects and participating in the constitution of an immunosuppressive microtumor environment. Clinical trials have found that the levels of MDSCs in the peripheral blood of cancer patients are strongly correlated with tumor stage, metastasis and prognosis. Moreover, animal experiments have confirmed that elimination of MDSCs inhibits tumor growth and metastasis to some extent. Therefore, MDSCs may become the target of immunotherapy for many cancers, and eliminating MDSCs can help improve the response rate to cancer treatment and patient survival. However, a clear definition of MDSCs and the specific mechanism involved in immune escape are lacking. In this paper, we review the role of the MDSCs population in tumor development and the mechanisms involved in immune escape in different tumor contexts. In addition, we discuss the use of these cells as targets for tumor immunotherapy. This review not only contributes to a systematic and comprehensive understanding of the essential role of MDSCs in immune system reactions against tumors but also provides information to guide the development of cancer therapies targeting MDSCs.
矛盾的是,肿瘤的发生和发展既可以被免疫系统抑制,也可以被其促进。经过免疫编辑的三个阶段,即清除、平衡和逃逸,肿瘤细胞不再受免疫监视的限制,从而发展为临床肿瘤。免疫逃逸的机制包括抗肿瘤相关免疫细胞异常、肿瘤细胞免疫抗性的选择、T细胞转运受损以及免疫抑制性肿瘤微环境的形成。一群独特的未成熟髓系细胞,即髓系来源的抑制细胞(MDSCs),主要通过发挥免疫抑制作用和参与免疫抑制性微肿瘤环境的构成来介导免疫逃逸。临床试验发现,癌症患者外周血中MDSCs的水平与肿瘤分期、转移及预后密切相关。此外,动物实验证实,清除MDSCs在一定程度上可抑制肿瘤生长和转移。因此,MDSCs可能成为多种癌症免疫治疗的靶点,清除MDSCs有助于提高癌症治疗的反应率和患者生存率。然而,目前缺乏对MDSCs的明确定义以及其参与免疫逃逸的具体机制。在本文中,我们综述了MDSCs群体在肿瘤发展中的作用以及不同肿瘤背景下免疫逃逸的相关机制。此外,我们还讨论了将这些细胞作为肿瘤免疫治疗靶点的应用。这篇综述不仅有助于系统全面地理解MDSCs在免疫系统抗肿瘤反应中的重要作用,还为指导针对MDSCs的癌症治疗发展提供了信息。