Apolipoprotein A1-Manipulated Cholesterol Efflux Subverts the Phagocytic Fragility of TAMs and Improves Oncolytic Viro-Immunotherapy in Glioblastoma [TAMs RNA-seq]

We found that TAMs in the glioblatoma (GBM) tumor microenvironment are enriched for cholesterol and highly express ABCA1/G1. To investigate the biological effects of enhancing cholesterol efflux of TAMs in GBM, we constructed APOA1-overexpressing GL261 cell line. We harvested tumor tissue and sorted these TAMs by anti-mouse F4/80 magnetic beads 17 days after intracranial transplantation of GL261-APOA1 cell line and control cells in immunocompetent C57 mice. Samples were subjected to transcriptome sequencing. Overall design: Comparative gene expression profiling analysis of RNA-seq data for TAMs sorted from GL261-APOA1 (n=4) or GL261-Puro (n=4) tumors

我们发现，胶质母细胞瘤（glioblastoma, GBM）肿瘤微环境中的肿瘤相关巨噬细胞（Tumor-associated macrophages, TAMs）富含胆固醇，且高表达ABCA1/G1。为探究增强GBM中TAMs胆固醇外流的生物学效应，我们构建了过表达APOA1的GL261细胞系。将GL261-APOA1与对照细胞颅内移植至免疫健全C57小鼠体内17天后，我们收集肿瘤组织，并通过抗小鼠F4/80磁珠分选获得上述TAMs。对样本进行转录组测序。整体实验设计：对从GL261-APOA1（n=4）或GL261-Puro（n=4）肿瘤中分选得到的TAMs的RNA测序数据开展比较基因表达谱分析。