摘要
Macroglia is a crucial macrophage only existing in the central nervous system.During the development of glioma,it can be activated as M2 anti-inflammatory type to promote glioma growth.Interferon-γ(IFN-γ)is an important immunomodulator in glioma microenvironment,which can also activate macroglia as M1 pro-inflammatory type to enhance anti-tumor immune response and lead to inhibition of glioma growth.Therefore,we utilized IFN-γto make macroglia maintain M1 phenotype,so that prospectively achieving anti-tumor immunity for glioma therapy.We prepared interferon-γ-liposomes(IFN-Lp)to protect IFN-γfrom elimination.IFN-Lp was proved to have strong capability to be phagocytosed and accumulate in macroglia(BV2 cells)to achieve long-term effect.In addition,IFN-Lp could allow BV2 cells to maintain M1 phenotype,showing no impact on its cell viability.These findings will offer new opportunities to achieve enhanced immunotherapy of glioma.
小胶质细胞是一种只存在于中枢神经系统中重要的巨噬细胞。它在脑胶质瘤进展中可以被激活为M2抗炎表型进而促进肿瘤的生长。干扰素-γ是胶质瘤微环境中一种重要的免疫调节因子,它可以将小胶质细胞激活为M1促炎表型,从而增强抗肿瘤免疫并导致肿瘤生长抑制。因此,我们利用干扰素-γ使小胶质细胞维持M1表型,有望实现抗肿瘤免疫的胶质瘤治疗。我们制备了干扰素脂质体以保护干扰素-γ不被清除。实验证明,干扰素脂质体具有很强的被小胶质细胞吞噬并蓄积于细胞内的能力,可以长期发挥药效。另外,干扰素脂质体可以使小胶质细胞维持M1表型,同时不影响细胞活性。这些研究成果将为增强胶质瘤免疫疗法提供新的机遇。
基金
National Nature Science Foundation of China(Grant No.81673365 and 81473156)