CD39/CD73 upregulation on myeloid-derived suppressor cells via TGF-β-mTOR-HIF-1 signaling in patients with non-small cell lung cancer

Jieyao Li; Liping Wang; Xinfeng Chen; Lifeng Li; Yu Li; Yu Ping; Lan Huang; Dongli Yue; Zhen Zhang; Fei Wang; Feng Li; Li Yang; Jianmin Huang; Shuangning Yang; Hong Li; Xuan Zhao; Wenjie Dong; Yan Yan; Song Zhao; Bo Huang; Bin Zhang; Yi Zhang

doi:10.1080/2162402X.2017.1320011

CD39/CD73 upregulation on myeloid-derived suppressor cells via TGF-β-mTOR-HIF-1 signaling in patients with non-small cell lung cancer

Jieyao Li, Liping Wang, Xinfeng Chen, Lifeng Li, Yu Li, Yu Ping, Lan Huang, Dongli Yue, Zhen Zhang, Fei Wang, Feng Li, Li Yang, Jianmin Huang, Shuangning Yang, Hong Li, Xuan Zhao, Wenjie Dong, Yan Yan, Song Zhao, Bo HuangBin Zhang^*, Yi Zhang

^*Corresponding author for this work

Medicine, Hematology Oncology Division

Research output: Contribution to journal › Article › peer-review

181 Scopus citations

Abstract

CD39/CD73-adenosine pathway has been recently defined as an important tumor-induced immunosuppressive mechanism. We here documented a fraction of CD11b⁺CD33⁺ myeloid-derived suppressor cells (MDSCs) in peripheral blood and tumor tissues from non-small cell lung cancer (NSCLC) patients expressed surface ectonucleotidases CD39 and CD73. Tumor TGF-β stimulated CD39 and CD73 expression, thereby inhibited T cell and NK cell activity, and protected tumor cells from the cytotoxic effect of chemotherapy through ectonucleotidase activity. Mechanistically, TGF-β triggered phosphorylation of mammalian target of rapamycin, and subsequently activated hypoxia-inducible factor-1α (HIF-1α) that induced CD39/CD73 expression on MDSCs. CD39 and CD73 on MDSCs, therefore, link their immunosuppressive and chemo-protective effects to NSCLC progression, providing novel targets for chemo-immunotherapeutic intervention.

Original language	English (US)
Article number	e1320011
Journal	OncoImmunology
Volume	6
Issue number	6
DOIs	https://doi.org/10.1080/2162402X.2017.1320011
State	Published - Jun 3 2017

Keywords

CD39
CD73
MDSCs
NSCLC
TGF-β

ASJC Scopus subject areas

Oncology
Immunology and Allergy
Immunology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1080/2162402X.2017.1320011

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Li, J., Wang, L., Chen, X., Li, L., Li, Y., Ping, Y., Huang, L., Yue, D., Zhang, Z., Wang, F., Li, F., Yang, L., Huang, J., Yang, S., Li, H., Zhao, X., Dong, W., Yan, Y., Zhao, S., ... Zhang, Y. (2017). CD39/CD73 upregulation on myeloid-derived suppressor cells via TGF-β-mTOR-HIF-1 signaling in patients with non-small cell lung cancer. OncoImmunology, 6(6), [e1320011]. https://doi.org/10.1080/2162402X.2017.1320011

@article{de043d5064eb408a84e934a306fe79ea,

title = "CD39/CD73 upregulation on myeloid-derived suppressor cells via TGF-β-mTOR-HIF-1 signaling in patients with non-small cell lung cancer",

abstract = "CD39/CD73-adenosine pathway has been recently defined as an important tumor-induced immunosuppressive mechanism. We here documented a fraction of CD11b+CD33+ myeloid-derived suppressor cells (MDSCs) in peripheral blood and tumor tissues from non-small cell lung cancer (NSCLC) patients expressed surface ectonucleotidases CD39 and CD73. Tumor TGF-β stimulated CD39 and CD73 expression, thereby inhibited T cell and NK cell activity, and protected tumor cells from the cytotoxic effect of chemotherapy through ectonucleotidase activity. Mechanistically, TGF-β triggered phosphorylation of mammalian target of rapamycin, and subsequently activated hypoxia-inducible factor-1α (HIF-1α) that induced CD39/CD73 expression on MDSCs. CD39 and CD73 on MDSCs, therefore, link their immunosuppressive and chemo-protective effects to NSCLC progression, providing novel targets for chemo-immunotherapeutic intervention.",

keywords = "CD39, CD73, MDSCs, NSCLC, TGF-β",

author = "Jieyao Li and Liping Wang and Xinfeng Chen and Lifeng Li and Yu Li and Yu Ping and Lan Huang and Dongli Yue and Zhen Zhang and Fei Wang and Feng Li and Li Yang and Jianmin Huang and Shuangning Yang and Hong Li and Xuan Zhao and Wenjie Dong and Yan Yan and Song Zhao and Bo Huang and Bin Zhang and Yi Zhang",

note = "Funding Information: We thank Yanyan Sun and Xiangnan Li for assistance in sample collecting. This study was supported by grants from the National Institutes of Health (CA149669 and CA208354), National Natural Science Foundation of China (Grant nos. 81171985 and 81171986), Research Grant from the Ministry of Public Health (No. 20110110001), the Basic and Advanced Technology Research Foundation from Science and Technology Department of Henan Province (Grant no.112300410153, Grant no.122300410155). Publisher Copyright: {\textcopyright} 2017 Taylor & Francis Group, LLC.",

year = "2017",

month = jun,

day = "3",

doi = "10.1080/2162402X.2017.1320011",

language = "English (US)",

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Li, J, Wang, L, Chen, X, Li, L, Li, Y, Ping, Y, Huang, L, Yue, D, Zhang, Z, Wang, F, Li, F, Yang, L, Huang, J, Yang, S, Li, H, Zhao, X, Dong, W, Yan, Y, Zhao, S, Huang, B, Zhang, B & Zhang, Y 2017, 'CD39/CD73 upregulation on myeloid-derived suppressor cells via TGF-β-mTOR-HIF-1 signaling in patients with non-small cell lung cancer', OncoImmunology, vol. 6, no. 6, e1320011. https://doi.org/10.1080/2162402X.2017.1320011

TY - JOUR

T1 - CD39/CD73 upregulation on myeloid-derived suppressor cells via TGF-β-mTOR-HIF-1 signaling in patients with non-small cell lung cancer

AU - Li, Jieyao

AU - Wang, Liping

AU - Chen, Xinfeng

AU - Li, Lifeng

AU - Li, Yu

AU - Ping, Yu

AU - Huang, Lan

AU - Yue, Dongli

AU - Zhang, Zhen

AU - Wang, Fei

AU - Li, Feng

AU - Yang, Li

AU - Huang, Jianmin

AU - Yang, Shuangning

AU - Li, Hong

AU - Zhao, Xuan

AU - Dong, Wenjie

AU - Yan, Yan

AU - Zhao, Song

AU - Huang, Bo

AU - Zhang, Bin

AU - Zhang, Yi

N1 - Funding Information: We thank Yanyan Sun and Xiangnan Li for assistance in sample collecting. This study was supported by grants from the National Institutes of Health (CA149669 and CA208354), National Natural Science Foundation of China (Grant nos. 81171985 and 81171986), Research Grant from the Ministry of Public Health (No. 20110110001), the Basic and Advanced Technology Research Foundation from Science and Technology Department of Henan Province (Grant no.112300410153, Grant no.122300410155). Publisher Copyright: © 2017 Taylor & Francis Group, LLC.

PY - 2017/6/3

Y1 - 2017/6/3

N2 - CD39/CD73-adenosine pathway has been recently defined as an important tumor-induced immunosuppressive mechanism. We here documented a fraction of CD11b+CD33+ myeloid-derived suppressor cells (MDSCs) in peripheral blood and tumor tissues from non-small cell lung cancer (NSCLC) patients expressed surface ectonucleotidases CD39 and CD73. Tumor TGF-β stimulated CD39 and CD73 expression, thereby inhibited T cell and NK cell activity, and protected tumor cells from the cytotoxic effect of chemotherapy through ectonucleotidase activity. Mechanistically, TGF-β triggered phosphorylation of mammalian target of rapamycin, and subsequently activated hypoxia-inducible factor-1α (HIF-1α) that induced CD39/CD73 expression on MDSCs. CD39 and CD73 on MDSCs, therefore, link their immunosuppressive and chemo-protective effects to NSCLC progression, providing novel targets for chemo-immunotherapeutic intervention.

AB - CD39/CD73-adenosine pathway has been recently defined as an important tumor-induced immunosuppressive mechanism. We here documented a fraction of CD11b+CD33+ myeloid-derived suppressor cells (MDSCs) in peripheral blood and tumor tissues from non-small cell lung cancer (NSCLC) patients expressed surface ectonucleotidases CD39 and CD73. Tumor TGF-β stimulated CD39 and CD73 expression, thereby inhibited T cell and NK cell activity, and protected tumor cells from the cytotoxic effect of chemotherapy through ectonucleotidase activity. Mechanistically, TGF-β triggered phosphorylation of mammalian target of rapamycin, and subsequently activated hypoxia-inducible factor-1α (HIF-1α) that induced CD39/CD73 expression on MDSCs. CD39 and CD73 on MDSCs, therefore, link their immunosuppressive and chemo-protective effects to NSCLC progression, providing novel targets for chemo-immunotherapeutic intervention.

KW - CD39

KW - CD73

KW - MDSCs

KW - NSCLC

KW - TGF-β

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U2 - 10.1080/2162402X.2017.1320011

DO - 10.1080/2162402X.2017.1320011

M3 - Article

C2 - 28680754

AN - SCOPUS:85019768282

SN - 2162-4011

VL - 6

JO - OncoImmunology

JF - OncoImmunology

IS - 6

M1 - e1320011

ER -

CD39/CD73 upregulation on myeloid-derived suppressor cells via TGF-β-mTOR-HIF-1 signaling in patients with non-small cell lung cancer

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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