干扰素-γ (IFN-γ)作为II型干扰素家族的核心成员,在肿瘤免疫调控中扮演着复杂的角色。一方面,IFN-γ可诱导肿瘤细胞凋亡、抑制血管生成、增强抗原呈递及细胞毒性T细胞功能,发挥显著的抗肿瘤作用。另一方面,低剂量或持续性的IFN-γ信号可促进肿瘤干细胞特性、上皮–间质转化(EMT)及免疫检查点分子(如PD-L1)的表达,加剧肿瘤转移与免疫逃逸。本文系统地综述了IFN-γ的双向调控机制,IFN-γ与巨噬细胞、T细胞及抗原呈递细胞的动态相互作用,及IFN-γ免疫检查点抑制剂治疗中的关键作用。IFN-γ相关基因的表达水平与免疫治疗疗效密切相关,但其促肿瘤特性却限制其在临床中的应用。未来研究需进一步解析IFN-γ在肿瘤微环境中的作用,探索其靶向调控信号通路的策略,以优化癌症免疫治疗的精准性与安全性。本文为理解IFN-γ的免疫调控网络及其在肿瘤治疗中的应用提供了新的视角。Interferon-γ (IFN-γ), a core member of the type II interferon family, plays a complex dual role in tumor immune regulation. On one hand, IFN-γ can induce apoptosis in tumor cells, inhibit angiogenesis, enhance antigen presentation, and promote cytotoxic T cell function, thereby exerting significant anti-tumor effects. On the other hand, low doses of IFN-γ or persistent IFN-γ signaling may exacerbate tumor metastasis and immune escape by promoting stem cell characteristics, epithelial-to-mesenchymal transition (EMT), and the expression of immune checkpoint molecules such as PD-L1. This paper systematically reviews the bidirectional regulatory mechanisms of IFN-γ, dynamic interactions with macrophages, T cells, and antigen-presenting cells, as well as its critical role in immune checkpoint inhibitor therapy. Research indicates that the expression levels of IFN-γ-related genes are closely related to the efficacy of immunotherapy, but its protumor characteristics may limit clinical benefits. Future studies should further dissect the role of IFN-γ within the tumor microenvironment and develop strategies for targeted modulation of its signaling pathways to enhance the precision and safety of cancer immunotherapy. This paper provides new insights into understanding the immune regulatory network of IFN-γ and its application in cancer treatment.
目的：基于网络药理学方法挖掘香青兰总黄酮治疗脑缺血/再灌注损伤（CIRI）的中药活性成分及其作用的主要靶点，运用分子对接探究活性成分与靶蛋白的结合能力，以期寻找高特异性的靶向改善CIRI的小分子药物。方法：依据TCMSP、HERB数据库及相关文献结合Pubchem、Swiss Institute of Bioinformatics筛选香青兰总黄酮主要活性成分的单体；GeneCards、OMIM及DisGeNET数据库筛选CIRI的相关靶点；运用jvenn筛选交集基因并绘制Venn图，STRING数据库绘制蛋白互作网络图；运用微生信平台及Metacape数据将交集基因进行GO、KEGG富集分析；将活性单体成分与核心基因进行分子对接。结果：香青兰总黄酮中筛选出活性单体成分20个，预测改善CIRI相关靶点2053个，GO及KEGG富集分析显示，香青兰总黄酮活性单体成分改善CIRI机制主要涉及对缺氧的反应、凋亡过程负向调控、炎症反应等生物过程，所涉及的通路包括氧化应激、细胞凋亡、PI3K-Akt等。结论：香青兰总黄酮改善CIRI具有多成分、多靶点的作用效果，其主要活性单体成分对不同靶点具有不同的结合能力，故提取高纯度的高特异性的活性单体成分可能提高香青兰总黄酮靶向改善CIRI的能力。
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