胶质瘤是脑部最常见的原发性恶性肿瘤，即使采用手术切除、放疗、化疗等标准治疗，患者的长期生存率仍不理想。复发是神经胶质瘤患者死亡的主要原因之一。神经胶质瘤复发的分子机制仍不清楚。我们的研究利用单细胞测序、空间转录组学和 RNA-seq 数据来鉴定与神经胶质瘤复发相关的 FN1  肿瘤相关巨噬细胞 (FN1  TAM) 的亚型。这项研究揭示了丰度增加FN1  TAMs 在复发性神经胶质瘤中的存在，表明它们可能是神经胶质瘤复发的关键因素。原发性胶质瘤中 FN1  TAM 的丰度与复发间隔时间呈负相关，提示 FN1  TAM 水平高的胶质瘤患者预后较差。进一步的研究表明，FN1  TAMs在缺氧肿瘤区域富集，这意味着肿瘤中的代谢变化驱动了FN1  TAMs的产生和募集。此外，FN1 TAM 被发现有助于调节神经胶质瘤中的免疫抑制微环境，其丰度可能作为患者对免疫治疗敏感性的指标。最后，我们开发了一个用户友好的网站 PRIMEG ( http://www.szflab.site/PRIMEG/ )，用于探索原发性和复发性胶质瘤的免疫微环境。我们的研究结果强调了与胶质瘤复发相关的 FN1   TAM 亚型，为潜在的治疗靶点提供新的见解。此外，丰富的 FN1  TAM 有望预测免疫治疗反应并帮助对复发性神经胶质瘤患者进行更精确的风险分层。© 2024。作者。

Glioma is the most common primary malignant tumor in the brain, and even with standard treatments including surgical resection, radiotherapy, and chemotherapy, the long-term survival rate of patients remains unsatisfactory. Recurrence is one of the leading causes of death in glioma patients. The molecular mechanisms underlying glioma recurrence remain unclear.Our study utilized single-cell sequencing, spatial transcriptomics, and RNA-seq data to identify a subtype of FN1 + tumor-associated macrophages (FN1 + TAMs) associated with glioma recurrence.This study revealed an increased abundance of FN1 + TAMs in recurrent gliomas, indicating their potential involvement as a critical factor in glioma recurrence. A negative correlation was observed between the abundance of FN1 + TAMs in primary gliomas and the interval time to recurrence, suggesting poor prognosis for glioma patients with high levels of FN1 + TAMs. Further investigation showed that FN1 + TAMs were enriched in hypoxic tumor regions, implying that metabolic changes in tumors drive the production and recruitment of FN1 + TAMs. Additionally, FN1 + TAMs were found to contribute to the regulation of an immunosuppressive microenvironment in gliomas, and their abundance might serve as an indicator of patients' sensitivity to immunotherapy. Finally, we developed a user-friendly website, PRIMEG ( http://www.szflab.site/PRIMEG/ ), for exploring the immune microenvironment of primary and recurrent gliomas.Our findings highlight a subtype of FN1 + TAMs associated with glioma recurrence, providing new insights into potential therapeutic targets. Moreover, the abundance of FN1 + TAMs hold promise for predicting immune therapy response and aiding in more precise risk stratification of recurrent glioma patients.© 2024. The Author(s).