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Bioprocess 2025
干扰素-γ在肿瘤免疫中的双重角色：抗肿瘤与促肿瘤作用
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Abstract:
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.
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