Zhao Rongrong, Pan Ziwen, Li Boyan, Zhao Shulin, Zhang Shouji, Qi Yanhua, Qiu Jiawei, Gao Zijie, Fan Yang, Guo Qindong, Qiu Wei, Wang Shaobo, Wang Qingtong, Zhang Ping, Guo Xing, Deng Lin, Xue Hao, Li Gang
Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan, China.
Shandong Key Laboratory of Brain Function Remodeling, Qilu Hospital, Shandong University, Jinan, China.
Front Immunol. 2022 Mar 2;13:820673. doi: 10.3389/fimmu.2022.820673. eCollection 2022.
Glioblastoma (GBM) is a fatal brain tumor with no effective treatment. The specific GBM tumor immune microenvironment (TIME) may contribute to resistance to immunotherapy, a tumor therapy with great potential. Thus, an in-depth understanding of the characteristics of tumor-infiltrating immune cells is essential for exploring biomarkers in GBM pathogenesis and immunotherapy.
We estimated the relative abundances of 25 immune cell types in 796 GBM samples using single sample gene set enrichment analysis (ssGSEA). Unsupervised clustering was used to identify different GBM-associated TIME immune cell infiltration (GTMEI) patterns. The GTMEIscore system was constructed with principal component analysis (PCA) to determine the immune infiltration pattern of individual tumors.
We revealed three distinct GTMEI patterns with different clinical outcomes and modulated biological pathways. We developed a scoring system (GTMEIscore) to determine the immune infiltration pattern of individual tumors. We comprehensively analyzed the genomic characteristics, molecular subtypes and clinicopathological features as well as proteomic, phosphoproteomic, acetylomic, lipidomic and metabolomic properties associated with the GTMEIscore and revealed many novel dysregulated pathways and precise targets in GBM. Moreover, the GTMEIscore accurately quantified the immune status of many other cancer types. Clinically, the GTMEIscore was found to have significant potential therapeutic value for chemotherapy/radiotherapy, immune checkpoint inhibitor (ICI) therapy and targeted therapy.
For the first time, we employed a multilevel and multiplatform strategy to construct a multidimensional molecular map of tumors with different immune infiltration patterns. These results may provide theoretical basises for identifying more effective predictive biomarkers and developing more effective drug combination strategies or novel immunotherapeutic agents for GBM.
胶质母细胞瘤（GBM）是一种致命的脑肿瘤，目前尚无有效治疗方法。GBM特定的肿瘤免疫微环境（TIME）可能导致其对免疫疗法产生抗性，而免疫疗法是一种具有巨大潜力的肿瘤治疗方法。因此，深入了解肿瘤浸润免疫细胞的特征对于探索GBM发病机制和免疫治疗中的生物标志物至关重要。
我们使用单样本基因集富集分析（ssGSEA）估计了796个GBM样本中25种免疫细胞类型的相对丰度。采用无监督聚类来识别不同的与GBM相关的TIME免疫细胞浸润（GTMEI）模式。利用主成分分析（PCA）构建GTMEI评分系统，以确定单个肿瘤的免疫浸润模式。
我们揭示了三种不同的GTMEI模式，它们具有不同的临床结局和调节的生物学途径。我们开发了一种评分系统（GTMEI评分）来确定单个肿瘤的免疫浸润模式。我们全面分析了与GTMEI评分相关的基因组特征、分子亚型和临床病理特征以及蛋白质组学、磷酸蛋白质组学、乙酰化蛋白质组学、脂质组学和代谢组学特性，揭示了GBM中许多新的失调途径和精确靶点。此外，GTMEI评分准确地量化了许多其他癌症类型的免疫状态。在临床上，发现GTMEI评分对化疗/放疗、免疫检查点抑制剂（ICI）治疗和靶向治疗具有显著的潜在治疗价值。
我们首次采用多层次和多平台策略构建了具有不同免疫浸润模式的肿瘤多维分子图谱。这些结果可能为识别更有效的预测生物标志物以及开发更有效的药物联合策略或新型GBM免疫治疗药物提供理论依据。
