Metformin-Induced Reduction of CD39 and CD73 Blocks Myeloid-Derived Suppressor Cell Activity in Patients with Ovarian Cancer
Lifeng Li, Liping Wang, Jieyao Li, Zhirui Fan, Li Yang, Zhen Zhang, Chaoqi Zhang, Dongli Yue, Guohui Qin, Tengfei Zhang, Feng Li, Xinfeng Chen, Yu Ping, Dan Wang, Qun Gao, Qianyi He, Lan Huang, Hong Li, Jianmin Huang, Xuan Zhao, Wenhua Xue, Zhi Sun, Jingli Lu, Jane J. Yu, Jie Zhao, Bin Zhang, Yi Zhang
The American Association for Cancer Research (AACR)
Published 2018
The American Association for Cancer Research (AACR)
Published 2018
| Publication Date: |
2018-04-03
|
|---|---|
| Publisher: |
The American Association for Cancer Research (AACR)
|
| Print ISSN: |
0008-5472
|
| Electronic ISSN: |
1538-7445
|
| Topics: |
Medicine
|
| Published by: |
| _version_ | 1836398874734886912 |
|---|---|
| autor | Lifeng Li, Liping Wang, Jieyao Li, Zhirui Fan, Li Yang, Zhen Zhang, Chaoqi Zhang, Dongli Yue, Guohui Qin, Tengfei Zhang, Feng Li, Xinfeng Chen, Yu Ping, Dan Wang, Qun Gao, Qianyi He, Lan Huang, Hong Li, Jianmin Huang, Xuan Zhao, Wenhua Xue, Zhi Sun, Jingli Lu, Jane J. Yu, Jie Zhao, Bin Zhang, Yi Zhang |
| beschreibung | Metformin is a broadly prescribed drug for type 2 diabetes that exerts antitumor activity, yet the mechanisms underlying this activity remain unclear. We show here that metformin treatment blocks the suppressive function of myeloid-derived suppressor cells (MDSC) in patients with ovarian cancer by downregulating the expression and ectoenzymatic activity of CD39 and CD73 on monocytic and polymononuclear MDSC subsets. Metformin triggered activation of AMP-activated protein kinase α and subsequently suppressed hypoxia-inducible factor α, which was critical for induction of CD39/CD73 expression in MDSC. Furthermore, metformin treatment correlated with longer overall survival in diabetic patients with ovarian cancer, which was accompanied by a metformin-induced reduction in the frequency of circulating CD39+CD73+ MDSC and a concomitant increase in the antitumor activities of circulating CD8+ T cells. Our results highlight a direct effect of metformin on MDSC and suggest that metformin may yield clinical benefit through improvement of antitumor T-cell immunity by dampening CD39/CD73-dependent MDSC immunosuppression in ovarian cancer patients.Significance: The antitumor activity of an antidiabetes drug is attributable to reduced immunosuppressive activity of myeloid-derived tumor suppressor cells. Cancer Res; 78(7); 1779–91. ©2018 AACR. |
| citation_standardnr | 6223994 |
| datenlieferant | ipn_articles |
| feed_id | 9360 |
| feed_publisher | The American Association for Cancer Research (AACR) |
| feed_publisher_url | http://www.aacr.org/ |
| insertion_date | 2018-04-03 |
| journaleissn | 1538-7445 |
| journalissn | 0008-5472 |
| publikationsjahr_anzeige | 2018 |
| publikationsjahr_facette | 2018 |
| publikationsjahr_intervall | 7984:2015-2019 |
| publikationsjahr_sort | 2018 |
| publisher | The American Association for Cancer Research (AACR) |
| quelle | Cancer Research |
| relation | http://cancerres.aacrjournals.org/content/78/7/1779.short?rss=1 |
| search_space | articles |
| shingle_author_1 | Lifeng Li, Liping Wang, Jieyao Li, Zhirui Fan, Li Yang, Zhen Zhang, Chaoqi Zhang, Dongli Yue, Guohui Qin, Tengfei Zhang, Feng Li, Xinfeng Chen, Yu Ping, Dan Wang, Qun Gao, Qianyi He, Lan Huang, Hong Li, Jianmin Huang, Xuan Zhao, Wenhua Xue, Zhi Sun, Jingli Lu, Jane J. Yu, Jie Zhao, Bin Zhang, Yi Zhang |
| shingle_author_2 | Lifeng Li, Liping Wang, Jieyao Li, Zhirui Fan, Li Yang, Zhen Zhang, Chaoqi Zhang, Dongli Yue, Guohui Qin, Tengfei Zhang, Feng Li, Xinfeng Chen, Yu Ping, Dan Wang, Qun Gao, Qianyi He, Lan Huang, Hong Li, Jianmin Huang, Xuan Zhao, Wenhua Xue, Zhi Sun, Jingli Lu, Jane J. Yu, Jie Zhao, Bin Zhang, Yi Zhang |
| shingle_author_3 | Lifeng Li, Liping Wang, Jieyao Li, Zhirui Fan, Li Yang, Zhen Zhang, Chaoqi Zhang, Dongli Yue, Guohui Qin, Tengfei Zhang, Feng Li, Xinfeng Chen, Yu Ping, Dan Wang, Qun Gao, Qianyi He, Lan Huang, Hong Li, Jianmin Huang, Xuan Zhao, Wenhua Xue, Zhi Sun, Jingli Lu, Jane J. Yu, Jie Zhao, Bin Zhang, Yi Zhang |
| shingle_author_4 | Lifeng Li, Liping Wang, Jieyao Li, Zhirui Fan, Li Yang, Zhen Zhang, Chaoqi Zhang, Dongli Yue, Guohui Qin, Tengfei Zhang, Feng Li, Xinfeng Chen, Yu Ping, Dan Wang, Qun Gao, Qianyi He, Lan Huang, Hong Li, Jianmin Huang, Xuan Zhao, Wenhua Xue, Zhi Sun, Jingli Lu, Jane J. Yu, Jie Zhao, Bin Zhang, Yi Zhang |
| shingle_catch_all_1 | Metformin-Induced Reduction of CD39 and CD73 Blocks Myeloid-Derived Suppressor Cell Activity in Patients with Ovarian Cancer Metformin is a broadly prescribed drug for type 2 diabetes that exerts antitumor activity, yet the mechanisms underlying this activity remain unclear. We show here that metformin treatment blocks the suppressive function of myeloid-derived suppressor cells (MDSC) in patients with ovarian cancer by downregulating the expression and ectoenzymatic activity of CD39 and CD73 on monocytic and polymononuclear MDSC subsets. Metformin triggered activation of AMP-activated protein kinase α and subsequently suppressed hypoxia-inducible factor α, which was critical for induction of CD39/CD73 expression in MDSC. Furthermore, metformin treatment correlated with longer overall survival in diabetic patients with ovarian cancer, which was accompanied by a metformin-induced reduction in the frequency of circulating CD39+CD73+ MDSC and a concomitant increase in the antitumor activities of circulating CD8+ T cells. Our results highlight a direct effect of metformin on MDSC and suggest that metformin may yield clinical benefit through improvement of antitumor T-cell immunity by dampening CD39/CD73-dependent MDSC immunosuppression in ovarian cancer patients.Significance: The antitumor activity of an antidiabetes drug is attributable to reduced immunosuppressive activity of myeloid-derived tumor suppressor cells. Cancer Res; 78(7); 1779–91. ©2018 AACR. Lifeng Li, Liping Wang, Jieyao Li, Zhirui Fan, Li Yang, Zhen Zhang, Chaoqi Zhang, Dongli Yue, Guohui Qin, Tengfei Zhang, Feng Li, Xinfeng Chen, Yu Ping, Dan Wang, Qun Gao, Qianyi He, Lan Huang, Hong Li, Jianmin Huang, Xuan Zhao, Wenhua Xue, Zhi Sun, Jingli Lu, Jane J. Yu, Jie Zhao, Bin Zhang, Yi Zhang The American Association for Cancer Research (AACR) 0008-5472 00085472 1538-7445 15387445 |
| shingle_catch_all_2 | Metformin-Induced Reduction of CD39 and CD73 Blocks Myeloid-Derived Suppressor Cell Activity in Patients with Ovarian Cancer Metformin is a broadly prescribed drug for type 2 diabetes that exerts antitumor activity, yet the mechanisms underlying this activity remain unclear. We show here that metformin treatment blocks the suppressive function of myeloid-derived suppressor cells (MDSC) in patients with ovarian cancer by downregulating the expression and ectoenzymatic activity of CD39 and CD73 on monocytic and polymononuclear MDSC subsets. Metformin triggered activation of AMP-activated protein kinase α and subsequently suppressed hypoxia-inducible factor α, which was critical for induction of CD39/CD73 expression in MDSC. Furthermore, metformin treatment correlated with longer overall survival in diabetic patients with ovarian cancer, which was accompanied by a metformin-induced reduction in the frequency of circulating CD39+CD73+ MDSC and a concomitant increase in the antitumor activities of circulating CD8+ T cells. Our results highlight a direct effect of metformin on MDSC and suggest that metformin may yield clinical benefit through improvement of antitumor T-cell immunity by dampening CD39/CD73-dependent MDSC immunosuppression in ovarian cancer patients.Significance: The antitumor activity of an antidiabetes drug is attributable to reduced immunosuppressive activity of myeloid-derived tumor suppressor cells. Cancer Res; 78(7); 1779–91. ©2018 AACR. Lifeng Li, Liping Wang, Jieyao Li, Zhirui Fan, Li Yang, Zhen Zhang, Chaoqi Zhang, Dongli Yue, Guohui Qin, Tengfei Zhang, Feng Li, Xinfeng Chen, Yu Ping, Dan Wang, Qun Gao, Qianyi He, Lan Huang, Hong Li, Jianmin Huang, Xuan Zhao, Wenhua Xue, Zhi Sun, Jingli Lu, Jane J. Yu, Jie Zhao, Bin Zhang, Yi Zhang The American Association for Cancer Research (AACR) 0008-5472 00085472 1538-7445 15387445 |
| shingle_catch_all_3 | Metformin-Induced Reduction of CD39 and CD73 Blocks Myeloid-Derived Suppressor Cell Activity in Patients with Ovarian Cancer Metformin is a broadly prescribed drug for type 2 diabetes that exerts antitumor activity, yet the mechanisms underlying this activity remain unclear. We show here that metformin treatment blocks the suppressive function of myeloid-derived suppressor cells (MDSC) in patients with ovarian cancer by downregulating the expression and ectoenzymatic activity of CD39 and CD73 on monocytic and polymononuclear MDSC subsets. Metformin triggered activation of AMP-activated protein kinase α and subsequently suppressed hypoxia-inducible factor α, which was critical for induction of CD39/CD73 expression in MDSC. Furthermore, metformin treatment correlated with longer overall survival in diabetic patients with ovarian cancer, which was accompanied by a metformin-induced reduction in the frequency of circulating CD39+CD73+ MDSC and a concomitant increase in the antitumor activities of circulating CD8+ T cells. Our results highlight a direct effect of metformin on MDSC and suggest that metformin may yield clinical benefit through improvement of antitumor T-cell immunity by dampening CD39/CD73-dependent MDSC immunosuppression in ovarian cancer patients.Significance: The antitumor activity of an antidiabetes drug is attributable to reduced immunosuppressive activity of myeloid-derived tumor suppressor cells. Cancer Res; 78(7); 1779–91. ©2018 AACR. Lifeng Li, Liping Wang, Jieyao Li, Zhirui Fan, Li Yang, Zhen Zhang, Chaoqi Zhang, Dongli Yue, Guohui Qin, Tengfei Zhang, Feng Li, Xinfeng Chen, Yu Ping, Dan Wang, Qun Gao, Qianyi He, Lan Huang, Hong Li, Jianmin Huang, Xuan Zhao, Wenhua Xue, Zhi Sun, Jingli Lu, Jane J. Yu, Jie Zhao, Bin Zhang, Yi Zhang The American Association for Cancer Research (AACR) 0008-5472 00085472 1538-7445 15387445 |
| shingle_catch_all_4 | Metformin-Induced Reduction of CD39 and CD73 Blocks Myeloid-Derived Suppressor Cell Activity in Patients with Ovarian Cancer Metformin is a broadly prescribed drug for type 2 diabetes that exerts antitumor activity, yet the mechanisms underlying this activity remain unclear. We show here that metformin treatment blocks the suppressive function of myeloid-derived suppressor cells (MDSC) in patients with ovarian cancer by downregulating the expression and ectoenzymatic activity of CD39 and CD73 on monocytic and polymononuclear MDSC subsets. Metformin triggered activation of AMP-activated protein kinase α and subsequently suppressed hypoxia-inducible factor α, which was critical for induction of CD39/CD73 expression in MDSC. Furthermore, metformin treatment correlated with longer overall survival in diabetic patients with ovarian cancer, which was accompanied by a metformin-induced reduction in the frequency of circulating CD39+CD73+ MDSC and a concomitant increase in the antitumor activities of circulating CD8+ T cells. Our results highlight a direct effect of metformin on MDSC and suggest that metformin may yield clinical benefit through improvement of antitumor T-cell immunity by dampening CD39/CD73-dependent MDSC immunosuppression in ovarian cancer patients.Significance: The antitumor activity of an antidiabetes drug is attributable to reduced immunosuppressive activity of myeloid-derived tumor suppressor cells. Cancer Res; 78(7); 1779–91. ©2018 AACR. Lifeng Li, Liping Wang, Jieyao Li, Zhirui Fan, Li Yang, Zhen Zhang, Chaoqi Zhang, Dongli Yue, Guohui Qin, Tengfei Zhang, Feng Li, Xinfeng Chen, Yu Ping, Dan Wang, Qun Gao, Qianyi He, Lan Huang, Hong Li, Jianmin Huang, Xuan Zhao, Wenhua Xue, Zhi Sun, Jingli Lu, Jane J. Yu, Jie Zhao, Bin Zhang, Yi Zhang The American Association for Cancer Research (AACR) 0008-5472 00085472 1538-7445 15387445 |
| shingle_title_1 | Metformin-Induced Reduction of CD39 and CD73 Blocks Myeloid-Derived Suppressor Cell Activity in Patients with Ovarian Cancer |
| shingle_title_2 | Metformin-Induced Reduction of CD39 and CD73 Blocks Myeloid-Derived Suppressor Cell Activity in Patients with Ovarian Cancer |
| shingle_title_3 | Metformin-Induced Reduction of CD39 and CD73 Blocks Myeloid-Derived Suppressor Cell Activity in Patients with Ovarian Cancer |
| shingle_title_4 | Metformin-Induced Reduction of CD39 and CD73 Blocks Myeloid-Derived Suppressor Cell Activity in Patients with Ovarian Cancer |
| timestamp | 2025-06-30T23:34:01.458Z |
| titel | Metformin-Induced Reduction of CD39 and CD73 Blocks Myeloid-Derived Suppressor Cell Activity in Patients with Ovarian Cancer |
| titel_suche | Metformin-Induced Reduction of CD39 and CD73 Blocks Myeloid-Derived Suppressor Cell Activity in Patients with Ovarian Cancer |
| topic | WW-YZ |
| uid | ipn_articles_6223994 |