Liu Xiao-Fei, Chang Yu-Jie, Long Min, Huang Kai-Qi, Wang Bing, Gong Duo, Luo Jun-Li, Feng Yong
Hengyang Medical School, University of South China, Hengyang, Hunan, China.
Department of Neurosurgery, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China.
J Cell Mol Med. 2025 Jul;29(13):e70697. doi: 10.1111/jcmm.70697.
Glioma, marked by a low mutational burden, low immunogenicity, high heterogeneity, and the challenges posed by the blood-brain barrier, continues to be a major hurdle in neuro-oncology. Current research underscores the necessity for more effective medications and treatment strategies. In this study, we explored the role of Apolipoprotein E (ApoE) in glioma using both bioinformatics and experimental methods. The construction of our bioinformatics risk model identified ApoE as a protective factor linked to longer survival in glioma patients. Subsequently, we created an in situ tumorigenic mouse model and a subcutaneous tumorigenic mouse model with ApoE gene knockout to evaluate the functional impacts of ApoE deficiency in glioma. Our results demonstrated that ApoE deficiency accelerates the growth of glioma and encourages the invasive behaviour of tumour cells into normal brain tissue. Additionally, we detected a reduction in the immune surveillance of glioma in the context of ApoE deficiency. Furthermore, flow cytometry analysis indicated that the lack of ApoE led to a decrease in positive immune cells and an increase in immunosuppressive cells within the tumour microenvironment. Our findings suggest that ApoE plays a crucial role in modulating glioma progression and immune surveillance, highlighting its potential as a therapeutic target.
胶质瘤具有低突变负荷、低免疫原性、高异质性以及血脑屏障带来的挑战，仍然是神经肿瘤学中的一个主要障碍。当前的研究强调了更有效药物和治疗策略的必要性。在本研究中，我们使用生物信息学和实验方法探索了载脂蛋白E（ApoE）在胶质瘤中的作用。我们的生物信息学风险模型构建确定ApoE是与胶质瘤患者更长生存期相关的保护因素。随后，我们创建了ApoE基因敲除的原位致瘤小鼠模型和皮下致瘤小鼠模型，以评估ApoE缺乏在胶质瘤中的功能影响。我们的结果表明，ApoE缺乏会加速胶质瘤的生长，并促进肿瘤细胞向正常脑组织的侵袭行为。此外，我们检测到在ApoE缺乏的情况下胶质瘤的免疫监视降低。此外，流式细胞术分析表明，ApoE的缺乏导致肿瘤微环境中阳性免疫细胞减少和免疫抑制细胞增加。我们的研究结果表明，ApoE在调节胶质瘤进展和免疫监视中起关键作用，突出了其作为治疗靶点的潜力。
