Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, PR China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, PR China.
Experiment Center of Medical Innovation, The First Hospital of Hunan University of Chinese Medicine, Changsha, 410007, Hunan, China.
Clin Immunol. 2024 Jan;258:109802. doi: 10.1016/j.clim.2023.109802. Epub 2023 Oct 20.
Oxidative stress dually affected cancer progression, while its effect on glioblastomas remained unclear. Herein, we clustered the multicenter glioblastoma cohorts based on the oxidative-stress-responsive genes (OSS) expression. We found that cluster 2 with high OSS levels suffered a worse prognosis. Functional analyses and immune-related analyses results exhibited that M2-like pro-tumoral macrophages and neutrophils were enriched in cluster 2, while Natural killer cells' infiltration was decreased. The increased M2-like pro-tumoral macrophages in cluster 2 was confirmed by immunofluorescence. An integrated single-cell analysis validated the malignant features of cluster 2 neoplastic cells and discovered their crosstalk with M2-like pro-tumoral macrophages. Moreover, we observed that SOD3 knockdown might decrease the M2-like pro-tumoral transformation of macrophage in vitro and in vivo. Comprehensively, we revealed oxidative stress' prognostic and immunosuppressive potential in glioblastoma and discovered SOD3's potential role in regulating macrophage M2-like pro-tumoral transformation.
氧化应激双重影响癌症进展，但其对脑胶质瘤的影响尚不清楚。在此，我们根据氧化应激反应基因（OSS）的表达对多中心脑胶质瘤队列进行聚类。我们发现，OSS 水平较高的聚类 2 预后较差。功能分析和免疫相关分析结果表明，M2 样促肿瘤巨噬细胞和中性粒细胞在聚类 2 中富集，而自然杀伤细胞浸润减少。免疫荧光证实了聚类 2 中增加的 M2 样促肿瘤巨噬细胞。整合的单细胞分析验证了聚类 2 肿瘤细胞的恶性特征，并发现了它们与 M2 样促肿瘤巨噬细胞的相互作用。此外，我们观察到 SOD3 敲低可能会减少体外和体内巨噬细胞的 M2 样促肿瘤转化。综上所述，我们揭示了氧化应激在脑胶质瘤中的预后和免疫抑制潜力，并发现了 SOD3 在调节巨噬细胞 M2 样促肿瘤转化中的潜在作用。
