Natural Coevolution of Tumor and Immunoenvironment in Glioblastoma

文献类型： 外文期刊

第一作者： Wu, Lingxiang

作者： Wu, Lingxiang;Wu, Wei;Zhu, Mengyan;Wu, Min;Du, Yuxin;Liu, Quanzhong;Li, Kening;Wang, Qianghu;Wu, Lingxiang;Wu, Wei;Li, Liangyu;Zhu, Mengyan;Wu, Min;Liu, Quanzhong;Wang, Ziyu;Li, Jie;Li, Kening;Zhang, Tingting;Cai, Yun;Liang, Yuan;Huang, Bin;Zhang, Ruohan;Lv, Sali;Wang, Qianghu;Wu, Lingxiang;Wu, Wei;Zhang, Junxia;Li, Liangyu;Zhu, Mengyan;Wu, Min;Liu, Quanzhong;Wang, Ziyu;Li, Jie;Li, Kening;Zhang, Tingting;Cai, Yun;Liang, Yuan;Huang, Bin;Qian, Xu;Lv, Sali;Wang, Qianghu;Zhou, Fengqi;Zhao, Zheng;Chai, Rui-Chao;Jiang, Tao;Zhang, Wei;Qiu, Xiaoguang;Jiang, Tao;Chen, Apeng;Chen, Apeng;Zou, Han;Srivastava, Rashmi;Jiang, Yinan;Xiao, Xiangwei;Zou, Han;Srivastava, Rashmi;Hu, Baoli;Jiang, Yinan;Xiao, Xiangwei;Lin, Fan;Lin, Fan;Hu, Lang;Wang, Xiuxing;Qian, Xu;Zheng, Siyuan;Zheng, Siyuan;Hu, Zhibin;Shen, Hongbing;Hu, Zhibin;Shen, Hongbing;Verhaak, Roel G. W.;Wang, Qianghu;Jiang, Tao;Verhaak, Roel G. W.;You, Yongping

作者机构：

期刊名称：CANCER DISCOVERY （ 影响因子：38.272； 五年影响因子：41.226 ）

ISSN： 2159-8274

年卷期： 2022 年 12 卷 12 期

页码：

收录情况： SCI

摘要： Isocitrate dehydrogenase (IDH) wild-type glioblastoma (GBM) has a dismal prog-nosis. A better understanding of tumor evolution holds the key to developing more effective treatment. Here we study GBM's natural evolutionary trajectory by using rare multifocal sam-ples. We sequenced 61,062 single cells from eight multifocal IDH wild-type primary GBMs and defi ned a natural evolution signature (NES) of the tumor. We show that the NES signifi cantly associates with the activation of transcription factors that regulate brain development, including MYBL2 and FOSL2. Hypoxia is involved in inducing NES transition potentially via activation of the HIF1A-FOSL2 axis. High-NES tumor cells could recruit and polarize bone marrow-derived macrophages through activation of the FOSL2-ANXA1-FPR1/3 axis. These polarized macrophages can effi ciently suppress T-cell activity and accelerate NES transition in tumor cells. Moreover, the polarized macrophages could upregulate CCL2 to induce tumor cell migration.SIGNIFICANCE: GBM progression could be induced by hypoxia via the HIF1A-FOSL2 axis. Tumor -derived ANXA1 is associated with recruitment and polarization of bone marrow-derived macrophages to suppress the immunoenvironment. The polarized macrophages promote tumor cell NES transition and migration.

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