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.
背景:阿尔茨海默病患者存在严重的脑能量障碍,近年来基于酮体干预的脑能量拯救策略在阿尔茨海默病的治疗中越来越受到重视。目的:探讨β-羟基丁酸能否改善β淀粉样蛋白1-42(β-amyloid protein 1-42,Aβ_(1-42))诱导的小鼠海马神经元HT2...
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背景:阿尔茨海默病患者存在严重的脑能量障碍,近年来基于酮体干预的脑能量拯救策略在阿尔茨海默病的治疗中越来越受到重视。目的:探讨β-羟基丁酸能否改善β淀粉样蛋白1-42(β-amyloid protein 1-42,Aβ_(1-42))诱导的小鼠海马神经元HT22细胞能量障碍。方法:将HT22细胞分为4组,分别为对照组、β-羟基丁酸组、Aβ_(1-42)组、Aβ_(1-42)+β-羟基丁酸组。使用相应试剂盒检测HT22细胞的存活率、ATP水平、α-酮戊二酸脱氢酶活性、Na^(+)K^(+)-ATP酶活性、线粒体膜电位及活性氧水平。结果与结论:与对照组相比,Aβ_(1-42)组HT22细胞的存活率、ATP水平、α-酮戊二酸脱氢酶活性、Na^(+)K^(+)-ATP酶活性、线粒体膜电位均显著降低(P<0.05),活性氧水平显著升高(P<0.05)。与Aβ_(1-42)组相比,Aβ_(1-42)+β-羟基丁酸组HT22细胞的存活率、ATP水平、α-酮戊二酸脱氢酶活性、Na^(+)K^(+)-ATP酶活性、线粒体膜电位均显著升高(P<0.05),活性氧水平显著降低(P<0.05)。结果表明:β-羟基丁酸提高了线粒体生物能量功能和细胞存活率,最终改善了Aβ_(1-42)诱导的HT22细胞能量障碍。
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