Li Xiao-Peng, Guo Zheng-Qian, Wang Bao-Feng, Zhao Min
Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Oncol. 2023 Aug 4;13:1236246. doi: 10.3389/fonc.2023.1236246. eCollection 2023.
The epidermal growth factor receptor (EGFR) is the most frequently altered gene in glioblastoma (GBM), which plays an important role in tumor development and anti-tumor immune response. While current molecular targeted therapies against the EGFR signaling pathway and its downstream key molecules have not demonstrated favorable clinical outcomes in GBM. Whereas tumor immunotherapies, especially immune checkpoint inhibitors, have shown durable antitumor responses in many cancers. However, the clinical efficacy is limited in patients carrying EGFR alterations, indicating that EGFR signaling may involve tumor immune response. Recent studies reveal that EGFR alterations not only promote GBM cell proliferation but also influence immune components in the tumor microenvironment (TME), leading to the recruitment of immunosuppressive cells (e.g., M2-like TAMs, MDSCs, and Tregs), and inhibition of T and NK cell activation. Moreover, EGFR alterations upregulate the expression of immunosuppressive molecules or cytokines (such as PD-L1, CD73, TGF-β). This review explores the role of EGFR alterations in establishing an immunosuppressive TME and hopes to provide a theoretical basis for combining targeted EGFR inhibitors with immunotherapy for GBM.
表皮生长因子受体（EGFR）是胶质母细胞瘤（GBM）中最常发生改变的基因，其在肿瘤发展和抗肿瘤免疫反应中起重要作用。虽然目前针对EGFR信号通路及其下游关键分子的分子靶向治疗在GBM中尚未显示出良好的临床效果。而肿瘤免疫疗法，尤其是免疫检查点抑制剂，已在许多癌症中显示出持久的抗肿瘤反应。然而，对于携带EGFR改变的患者，临床疗效有限，这表明EGFR信号可能涉及肿瘤免疫反应。最近的研究表明，EGFR改变不仅促进GBM细胞增殖，还影响肿瘤微环境（TME）中的免疫成分，导致免疫抑制细胞（如M2样肿瘤相关巨噬细胞、髓源性抑制细胞和调节性T细胞）的募集，并抑制T细胞和自然杀伤细胞的激活。此外，EGFR改变上调免疫抑制分子或细胞因子（如程序性死亡受体配体1、CD73、转化生长因子-β）的表达。本综述探讨了EGFR改变在建立免疫抑制性TME中的作用，希望为将EGFR靶向抑制剂与GBM免疫疗法联合应用提供理论依据。
