scRNA-seq和蛋白质组学揭示了m2样巨噬细胞在原发性和

2023年5月，福建医科大学附属医院神经外科;福建医科大学附属医院福建省妇儿医院妇科;莆田学院附属医院神经外科;福州平潭综合实验区医院 (Department of Neurosurgery, Fujian Medical University Union Hospital,Fuzhou, China；Fujian Medical University, Fuzhou, China；Department of Gynaecology, Fujian Provincial Maternity and Children's Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, China；Department of Neurosurgery, Affiliated Hospital of Putian University, Putian,China；Pingtan Comprehensive Experimental Area Hospital, Fuzhou, China) Guiting You老师研究团队在《CNS Neuroscience & Therapeutics》上发表论文：

“scRNA-seq and proteomics reveal the distinction of M2-like macrophages between primary and recurrent malignant glioma and its critical role in the recurrence"

“scRNA-seq和蛋白质组学揭示了m2样巨噬细胞在原发性和复发性恶性胶质瘤中的差异及其在复发中的关键作用"

Abstract：

Aims: Tumor-associated macrophages (TAMs) in the immune microenvironment play an important role in the increased drug resistance and recurrence of malignant glioma, but the mechanism remains incompletely inventoried. The focus of this study was to investigate the distinctions of M2-like TAMs in the immune microenvironment between primary and recurrent malignant glioma and its influence in the recurrence.

Methods: We employed single-cell RNA sequencing to construct a single-cell atlas for a total of 23,010 individual cells from 6 patients with primary or recurrent malignant glioma and identified 5 cell types, including TAMs and malignant cells. Immunohistochemical techniques and proteomics analysis were performed to investigate the role of intercellular interaction between malignant cells and TAMs in the recurrence of malignant glioma.

Results: Six subgroups of TAMs were annotated and M2-like TAMs were found to increase in recurrent malignant glioma significantly. A pseudotime trajectory and a dynamic gene expression profiling during the recurrence of malignant glioma were reconstructed. Up-regulation of several cancer pathways and intercellular interaction-related genes are associated with the recurrence of malignant glioma. Moreover, the M2-like TAMs can activate the PI3K/Akt/HIF-1α/CA9 pathway in the malignant glioma cells via SPP1-CD44-mediated intercellular interaction. Interestingly, high expression of CA9 can trigger the immunosuppressive response in the malignant glioma, thus promoting the degree of malignancy and drug resistance.

Conclusion: Our study uncovers the distinction of M2-like TAMs between primary and recurrent glioma, which offers unparalleled insights into the immune microenvironment of primary and recurrent malignant glioma.

摘要：

目的:免疫微环境中的肿瘤相关巨噬细胞(Tumor-associated macrophages, tam)在恶性胶质瘤耐药增加和复发中发挥重要作用，但其机制尚不全清楚。本研究的重点是探讨原发性和复发性恶性胶质瘤免疫微环境中m2样tam的差异及其对复发的影响。

方法:采用单细胞RNA测序技术，构建来自6例原发性或复发性恶性胶质瘤患者的23,010个细胞的单细胞图谱，鉴定出包括tam细胞和恶性细胞在内的5种细胞类型。通过免疫组织化学技术和蛋白质组学分析，研究恶性细胞与tam之间的细胞间相互作用在恶性胶质瘤复发中的作用。

结果:6个tam亚组被注释，发现复发性恶性胶质瘤中m2样tam显著增加。重建恶性胶质瘤复发期间的假时间轨迹和动态基因表达谱。几种肿瘤通路和细胞间相互作用相关基因的上调与恶性胶质瘤的复发有关。此外，m2样tam可以通过spp1 - cd44介导的细胞间相互作用激活恶性胶质瘤细胞中的PI3K/Akt/HIF-1α/CA9通路。有趣的是，在恶性胶质瘤中，CA9的高表达可引发免疫抑制反应，从而促进恶性程度和耐药。

结论:研究人员的研究揭示了原发性和复发性胶质瘤之间m2样tam的差异，为原发性和复发性恶性胶质瘤的免疫微环境提供了的见解。

该论文中，人胶质瘤U87细胞及其慢病毒转染细胞的体外培养是使用Ausbian特级胎牛血清完成的。