Natural Coevolution of Tumor and Immunoenvironment in Glioblastoma. Wu, L., Wu, W., Zhang, J., Zhao, Z., Li, L., Zhu, M., Wu, M., Wu, F., Zhou, F., Du, Y., Chai, R. C., Zhang, W., Qiu, X., Liu, Q., Wang, Z., Li, J., Li, K., Chen, A., Jiang, Y., Xiao, X., Zou, H., Srivastava, R., Zhang, T., Cai, Y., Liang, Y., Huang, B., Zhang, R., Lin, F., Hu, L., Wang, X., Qian, X., Lv, S., Hu, B., Zheng, S., Hu, Z., Shen, H., You, Y., Verhaak, R. G. W., Jiang, T., & Wang, Q. Cancer Discov, 12(12):2820-2837, 2022. 2159-8290 Wu, Lingxiang Orcid: 0000-0003-4319-7862 Wu, Wei Orcid: 0000-0002-6228-0605 Zhang, Junxia Orcid: 0000-0003-1622-8045 Zhao, Zheng Orcid: 0000-0001-8945-9632 Li, Liangyu Orcid: 0000-0002-3540-7551 Zhu, Mengyan Orcid: 0000-0003-2953-8309 Wu, Min Orcid: 0000-0002-8779-7782 Wu, Fan Orcid: 0000-0001-9256-0176 Zhou, Fengqi Orcid: 0000-0003-4070-8153 Du, Yuxin Orcid: 0000-0001-7429-3238 Chai, Rui-Chao Orcid: 0000-0003-3451-8871 Zhang, Wei Orcid: 0000-0001-7800-3189 Qiu, Xiaoguang Orcid: 0000-0002-6806-9827 Liu, Quanzhong Orcid: 0000-0003-4248-3285 Wang, Ziyu Orcid: 0000-0002-1570-0152 Li, Jie Orcid: 0000-0001-5905-3359 Li, Kening Orcid: 0000-0001-9750-1810 Chen, Apeng Orcid: 0000-0002-1936-2007 Jiang, Yinan Orcid: 0000-0001-5644-6261 Xiao, Xiangwei Orcid: 0000-0003-0890-9203 Zou, Han Orcid: 0000-0002-3574-3379 Srivastava, Rashmi Orcid: 0000-0002-8773-3973 Zhang, Tingting Orcid: 0000-0002-8345-4897 Cai, Yun Orcid: 0000-0002-5402-8143 Liang, Yuan Orcid: 0000-0002-9143-9670 Huang, Bin Orcid: 0000-0003-4602-1782 Zhang, Ruohan Orcid: 0000-0002-7099-7067 Lin, Fan Orcid: 0000-0001-9169-9416 Hu, Lang Orcid: 0000-0001-7627-652x Wang, Xiuxing Orcid: 0000-0002-5993-9368 Qian, Xu Orcid: 0000-0003-1533-8568 Lv, Sali Orcid: 0000-0002-5159-5062 Hu, Baoli Orcid: 0000-0002-2737-6871 Zheng, Siyuan Orcid: 0000-0002-1031-9424 Hu, Zhibin Orcid: 0000-0002-8277-5234 Shen, Hongbing Orcid: 0000-0002-2581-5906 You, Yongping Orcid: 0000-0003-4753-5515 Verhaak, Roel G W Orcid: 0000-0003-2773-0436 Jiang, Tao Orcid: 0000-0002-7008-6351 Wang, Qianghu Orcid: 0000-0002-3488-1059 Journal Article Research Support, Non-U.S. Gov't United States 2022/09/20 Cancer Discov. 2022 Dec 2;12(12):2820-2837. doi: 10.1158/2159-8290.CD-22-0196.
doi  abstract   bibtex   
Isocitrate dehydrogenase (IDH) wild-type glioblastoma (GBM) has a dismal prognosis. 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 samples. We sequenced 61,062 single cells from eight multifocal IDH wild-type primary GBMs and defined a natural evolution signature (NES) of the tumor. We show that the NES significantly 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 efficiently 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. This article is highlighted in the In This Issue feature, p. 2711.
@article{RN6055,
   author = {Wu, L. and Wu, W. and Zhang, J. and Zhao, Z. and Li, L. and Zhu, M. and Wu, M. and Wu, F. and Zhou, F. and Du, Y. and Chai, R. C. and Zhang, W. and Qiu, X. and Liu, Q. and Wang, Z. and Li, J. and Li, K. and Chen, A. and Jiang, Y. and Xiao, X. and Zou, H. and Srivastava, R. and Zhang, T. and Cai, Y. and Liang, Y. and Huang, B. and Zhang, R. and Lin, F. and Hu, L. and Wang, X. and Qian, X. and Lv, S. and Hu, B. and Zheng, S. and Hu, Z. and Shen, H. and You, Y. and Verhaak, R. G. W. and Jiang, T. and Wang, Q.},
   title = {Natural Coevolution of Tumor and Immunoenvironment in Glioblastoma},
   journal = {Cancer Discov},
   volume = {12},
   number = {12},
   pages = {2820-2837},
   note = {2159-8290
Wu, Lingxiang
Orcid: 0000-0003-4319-7862
Wu, Wei
Orcid: 0000-0002-6228-0605
Zhang, Junxia
Orcid: 0000-0003-1622-8045
Zhao, Zheng
Orcid: 0000-0001-8945-9632
Li, Liangyu
Orcid: 0000-0002-3540-7551
Zhu, Mengyan
Orcid: 0000-0003-2953-8309
Wu, Min
Orcid: 0000-0002-8779-7782
Wu, Fan
Orcid: 0000-0001-9256-0176
Zhou, Fengqi
Orcid: 0000-0003-4070-8153
Du, Yuxin
Orcid: 0000-0001-7429-3238
Chai, Rui-Chao
Orcid: 0000-0003-3451-8871
Zhang, Wei
Orcid: 0000-0001-7800-3189
Qiu, Xiaoguang
Orcid: 0000-0002-6806-9827
Liu, Quanzhong
Orcid: 0000-0003-4248-3285
Wang, Ziyu
Orcid: 0000-0002-1570-0152
Li, Jie
Orcid: 0000-0001-5905-3359
Li, Kening
Orcid: 0000-0001-9750-1810
Chen, Apeng
Orcid: 0000-0002-1936-2007
Jiang, Yinan
Orcid: 0000-0001-5644-6261
Xiao, Xiangwei
Orcid: 0000-0003-0890-9203
Zou, Han
Orcid: 0000-0002-3574-3379
Srivastava, Rashmi
Orcid: 0000-0002-8773-3973
Zhang, Tingting
Orcid: 0000-0002-8345-4897
Cai, Yun
Orcid: 0000-0002-5402-8143
Liang, Yuan
Orcid: 0000-0002-9143-9670
Huang, Bin
Orcid: 0000-0003-4602-1782
Zhang, Ruohan
Orcid: 0000-0002-7099-7067
Lin, Fan
Orcid: 0000-0001-9169-9416
Hu, Lang
Orcid: 0000-0001-7627-652x
Wang, Xiuxing
Orcid: 0000-0002-5993-9368
Qian, Xu
Orcid: 0000-0003-1533-8568
Lv, Sali
Orcid: 0000-0002-5159-5062
Hu, Baoli
Orcid: 0000-0002-2737-6871
Zheng, Siyuan
Orcid: 0000-0002-1031-9424
Hu, Zhibin
Orcid: 0000-0002-8277-5234
Shen, Hongbing
Orcid: 0000-0002-2581-5906
You, Yongping
Orcid: 0000-0003-4753-5515
Verhaak, Roel G W
Orcid: 0000-0003-2773-0436
Jiang, Tao
Orcid: 0000-0002-7008-6351
Wang, Qianghu
Orcid: 0000-0002-3488-1059
Journal Article
Research Support, Non-U.S. Gov't
United States
2022/09/20
Cancer Discov. 2022 Dec 2;12(12):2820-2837. doi: 10.1158/2159-8290.CD-22-0196.},
   abstract = {Isocitrate dehydrogenase (IDH) wild-type glioblastoma (GBM) has a dismal prognosis. 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 samples. We sequenced 61,062 single cells from eight multifocal IDH wild-type primary GBMs and defined a natural evolution signature (NES) of the tumor. We show that the NES significantly 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 efficiently 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. This article is highlighted in the In This Issue feature, p. 2711.},
   keywords = {Humans
*Glioblastoma/genetics/pathology
*Brain Neoplasms/genetics/pathology
Isocitrate Dehydrogenase/genetics
Prognosis
Hypoxia/genetics},
   ISSN = {2159-8274 (Print)
2159-8274},
   DOI = {10.1158/2159-8290.Cd-22-0196},
   year = {2022},
   type = {Journal Article}
}

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