Natural Coevolution of Tumor and Immunoenvironment in Glioblastoma

被引：80

作者：

Wu, Lingxiang ^{[1
,2
,3
]}

Wu, Wei ^{[1
,2
,3
]}

Zhang, Junxia ^{[3
]}

Zhao, Zheng ^{[5
]}

Li, Liangyu ^{[2
,3
]}

Zhu, Mengyan ^{[1
,2
,3
]}

Wu, Min ^{[1
,2
,3
]}

Wu, Fan

Zhou, Fengqi ^{[4
]}

Du, Yuxin ^{[1
]}

Chai, Rui-Chao ^{[5
]}

Zhang, Wei ^{[6
]}

Qiu, Xiaoguang ^{[6
]}

Liu, Quanzhong ^{[1
,2
,3
]}

Wang, Ziyu ^{[2
,3
]}

Li, Jie ^{[2
,3
]}

Li, Kening ^{[1
,2
,3
]}

Chen, Apeng ^{[7
,8
]}

Jiang, Yinan ^{[9
,10
]}

Xiao, Xiangwei ^{[9
,10
]}

Zou, Han ^{[8
,9
]}

Srivastava, Rashmi ^{[8
,9
]}

Zhang, Tingting ^{[2
,3
]}

Cai, Yun ^{[2
,3
]}

Liang, Yuan ^{[2
,3
]}

Huang, Bin ^{[2
,3
]}

Zhang, Ruohan ^{[2
]}

Lin, Fan ^{[11
,12
]}

Hu, Lang ^{[13
]}

Wang, Xiuxing ^{[13
]}

Qian, Xu ^{[3
,14
]}

Lv, Sali ^{[2
,3
]}

Hu, Baoli ^{[9
]}

Zheng, Siyuan ^{[15
,16
]}

Hu, Zhibin ^{[17
,18
]}

Shen, Hongbing ^{[17
,18
]}

You, Yongping ^{[23
]}

Verhaak, Roel G. W. ^{[19
,22
]}

Jiang, Tao ^{[5
,6
,21
]}

Wang, Qianghu ^{[1
,2
,3
,20
]}

机构：

[1] Nanjing Med Univ, Jiangsu Canc Hosp, Jiangsu Inst Canc Res, Affiliated Canc Hosp, Nanjing, Peoples R China

[2] Nanjing Med Univ, Dept Bioinformat, Nanjing, Peoples R China

[3] Nanjing Med Univ, Inst Brain Tumors, Jiangsu Collaborat Innovat Ctr Canc Personalized M, Nanjing, Peoples R China

[4] Nanjing Med Univ, Dept Neurosurg, Affiliated Hosp 1, Nanjing, Peoples R China

[5] Capital Med Univ, Beijing Neurosurg Inst, Beijing, Peoples R China

[6] Capital Med Univ, Beijing Tiantan Hosp, Beijing, Peoples R China

[7] Chinese Acad Agr Sci, Lanzhou Vet Res Inst, State Key Lab Vet Etiol Biol, Lanzhou, Peoples R China

[8] Univ Pittsburgh, Dept Neurol Surg, Sch Med, Pittsburgh, PA USA

[9] Univ Pittsburgh Med Ctr UPMC, Res Ctr, Childrens Hosp Pittsburgh, Pittsburgh, PA USA

[10] Univ Pittsburgh, Dept Pediat Surg, Sch Med, Pittsburgh, PA USA

[11] Nanjing Med Univ, Sch Basic Med Sci, Dept Cell Biol, Nanjing, Peoples R China

[12] Nanjing Med Univ, Inst Brain Tumors, Key Lab Rare Metab Dis, Nanjing, Peoples R China

[13] Nanjing Med Univ, Sch Basic Med Sci, Nanjing, Peoples R China

[14] Nanjing Med Univ, Ctr Global Hlth, Sch Publ Hlth, Dept Nutr & Food Hyg, Nanjing, Peoples R China

[15] UT Hlth San Antonio, Greehey Childrens Canc Res Inst, San Antonio, TX USA

[16] UT Hlth San Antonio, Dept Populat Hlth Sci, San Antonio, TX USA

[17] Nanjing Med Univ, Collaborat Innovat Ctr Canc Med, Jiangsu Key Lab Canc Biomarkers Prevent & Treatmen, Nanjing, Peoples R China

[18] Nanjing Med Univ, Int Joint Res Ctr Environm & Human Hlth, Ctr Global Hlth, Sch Publ Hlth,Dept Epidemiol & Biostat, Nanjing, Peoples R China

[19] Jackson Lab Genom Med, Farmington, CT USA

[20] Nanjing Med Univ, Nanjing 211166, Peoples R China

[21] Capital Med Univ, Beijing Tiantan Hosp, Beijing Neurosurg Inst, Beijing 100070, Peoples R China

[22] Jackson Lab Genom Med, Farmington, CT 06032 USA

[23] Nanjing Med Univ, Dept Neurosurg, Affiliated Hosp 1, Nanjing 210029, Peoples R China

来源：

CANCER DISCOVERY | 2022年 / 12卷 / 12期

基金：

中国国家自然科学基金;

关键词：

CLONAL EVOLUTION; SUBTYPES; REVEALS; MANAGEMENT;

D O I：

10.1158/2159-8290.CD-22-0196

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

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.

引用

页码：2820 / 2837

页数：18

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