Glioma promotes macrophage immunosuppressive phenotype through ANXA1 in a methionine metabolism-dependent manner

作者：Hong Hu, Yulian Huang, Jiafeng Li, Ruijie Liu, Honglei Li, Meng Cai, Hao Chen, Ning Wang, Shuo Yang, Kaikai Wang, Lei Teng, Huailei Liu · 发表于：Discover Oncology · 年份：2025 · DOI：10.1007/s12672-025-03112-y · 被引用次数：6 · 研究领域：Immune cells in cancer、Cancer, Hypoxia, and Metabolism、Ferroptosis and cancer prognosis

In gliomas, particularly in glioblastoma (GBM), the tumor immunosuppressive microenvironment is widely recognized as a significant obstacle to effective treatment, contributing to reduced survival rates and the failure of targeted therapies and chemotherapy. Methionine (Met) is an essential amino acid in human metabolism and plays a crucial role in the development of glioma. However, the role of Met metabolism in the formation of the tumor immunosuppression microenvironment remains uncertain. In this study, we investigated the feature of Met metabolism in gliomas and its relationship with the tumor immune microenvironment. First, we began with the overall cohort of glioma patients. Through methionine metabolism activity scoring (MMA-score) of glioma cohorts, we observed a significant positive correlation between MMA-score and glioma WHO grades. Further analysis revealed that tumors with high MMA-scores exhibit more immunosuppressive microenvironment characteristics, including significantly increased infiltration of M2-type macrophages. Subsequently, single-cell RNA sequencing (scRNA-seq) analysis revealed that glioma cells exhibit dominant methionine metabolism activity within the tumor microenvironment, significantly surpassing that of other cell types. This suggests that glioma cells are likely the primary contributors to the overall methionine metabolic activity observed in tumors. Moreover, distinct heterogeneity in methionine metabolism was observed among glioma cells of...