中枢神经系统胆固醇代谢及其对脑胶质瘤免疫治疗的作用

Cholesterol Metabolism in Central Nervous System and Its Role in Glioma

脑胶质瘤是中枢神经系统最常见的原发性恶性肿瘤,精准手术、放疗和化疗联合下的综合治疗效果并不十分理想。近年来,免疫治疗在肿瘤领域取得了一些突破性进展,包括PD-1/PD-L1抑制剂、肿瘤特异性疫苗、过继性T细胞疗法、溶瘤病毒等的治疗方法在恶性肿瘤治疗领域中进展迅速。但脑胶质瘤的特殊微环境以及免疫转运的阻碍,免疫治疗在脑胶质瘤治疗领域的前期研究结果并不乐观。胆固醇是一种广泛存在于动物体内的小分子脂类物质,对于维持细胞的活性与功能至关重要。胆固醇代谢可以通过激活多个信号通路产生多种生物活性中间体,后者可以调节多个信号通路,在调节细胞生长、增殖、分化、存活、凋亡、炎症、运动和细胞膜稳态等方面发挥重要作用。胆固醇在人体内以脑和神经组织分布最为丰富,中枢神经系统胆固醇代谢对免疫功能影响的深入研究或许会成为脑胶质瘤免疫治疗的突破口。

Glioma is the most common primary malignant tumor in the central nervous system. The combined treatment of precise surgery, radiotherapy and chemotherapy is not good enough. Recently, immunotherapy has made a revolutionary breakthrough in cancer, including PD-1/PD-L1 inhibitors, tumor specific vaccines, adoptive T-cell therapy, oncolytic virus and so on. However, due to the special microenvironment of glioma and the hindrance of immune transport, the early research results of glioma immunotherapy are not optimistic. Cholesterol is a kind of small molecule lipid which widely exists in animals, and essential to maintain the activity and function of cells. Cholesterol metabolism can produce a variety of bioactive intermediates by activating multiple signaling pathways. The latter can regulate multiple signaling pathways and play an important role in regulating cell growth, proliferation, differentiation, survival, apoptosis, inflammation, movement and cell membrane homeostasis. In human body, most of the cholesterol distributes in brain and nervous tissue. In-depth study on the effects of cholesterol metabolism in the immune of central nervous system may be a breakthrough in glioma immunotherapy.