Li Jin-Wei, Mao Yi-Ming, Chen Shi-Liang, Ye Rui, Fei Yi-Ran, Li Yue, Tong Shi-Yuan, Yang Hong-Wei, He Yi-Bo
Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
Department of Thoracic Surgery, Suzhou Kowloon Hospital, Shanghai Jiao Tong University School of Medicine, Suzhou, Jiangsu Province, China.
Discov Oncol. 2024 Aug 12;15(1):348. doi: 10.1007/s12672-024-01229-0.
This review explores the intricate roles of metal ions-iron, copper, zinc, and selenium-in glioma pathogenesis and immune evasion. Dysregulated metal ion metabolism significantly contributes to glioma progression by inducing oxidative stress, promoting angiogenesis, and modulating immune cell functions. Iron accumulation enhances oxidative DNA damage, copper activates hypoxia-inducible factors to stimulate angiogenesis, zinc influences cell proliferation and apoptosis, and selenium modulates the tumor microenvironment through its antioxidant properties. These metal ions also facilitate immune escape by upregulating immune checkpoints and secreting immunosuppressive cytokines. Targeting metal ion pathways with therapeutic strategies such as chelating agents and metalloproteinase inhibitors, particularly in combination with conventional treatments like chemotherapy and immunotherapy, shows promise in improving treatment efficacy and overcoming resistance. Future research should leverage advanced bioinformatics and integrative methodologies to deepen the understanding of metal ion-immune interactions, ultimately identifying novel biomarkers and therapeutic targets to enhance glioma management and patient outcomes.
本综述探讨了金属离子(铁、铜、锌和硒)在胶质瘤发病机制和免疫逃逸中的复杂作用。金属离子代谢失调通过诱导氧化应激、促进血管生成和调节免疫细胞功能,显著促进胶质瘤进展。铁积累会增强氧化性DNA损伤,铜激活缺氧诱导因子以刺激血管生成,锌影响细胞增殖和凋亡,而硒则通过其抗氧化特性调节肿瘤微环境。这些金属离子还通过上调免疫检查点和分泌免疫抑制细胞因子促进免疫逃逸。采用螯合剂和金属蛋白酶抑制剂等治疗策略靶向金属离子途径,特别是与化疗和免疫疗法等传统治疗方法联合使用,有望提高治疗效果并克服耐药性。未来的研究应利用先进的生物信息学和综合方法,加深对金属离子与免疫相互作用的理解,最终确定新的生物标志物和治疗靶点以改善胶质瘤管理和患者预后。