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Hypoxia induces T-cell apoptosis by inhibiting chemokine C receptor 7 expression: the role of adenosine receptor A2

Cellular & Molecular Immunology volume 7, pages 77–82 (2010)Cite this article

Abstract

Hypoxia is a major characteristic of the tumor microenvironment, and its effects on immune cells are proposed to be important factors for the process of tumor immune escape. It has been reported that hypoxia affects the function of dendritic cells and the antitumor function of T cells. Here we discuss the effects of hypoxia on T-cell survival. Our results showed that hypoxia induced apoptosis of T cells. Adenosine and adenosine receptors (AR) are important to the hypoxia-related signaling pathway. Using AR agonists and antagonists, we demonstrated that hypoxia-induced apoptosis of T cells was mediated by A2a and A2b receptors. Furthermore, we are the first, to our knowledge, to report that hypoxia significantly inhibited the expression of chemokine C receptor 7 (CCR7) of T cells via the A2R signal pathway, perhaps representing a mechanism of hypoxia-induced apoptosis of T cells. Collectively, our research demonstrated that hypoxia induces T-cell apoptosis by the A2R signaling pathway partly by suppressing CCR7. Blocking the A2R signaling pathway and/or activation of CCR7 can increase the anti-apoptosis function of T cells and may become a new strategy to improve antitumor potential.

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (No. 30671902 and No. 30872321) and the Natural Science Foundation of Shandong Province (No. Y2008C02 and No. Y2006C122).

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Author notes

  1. Jintang Sun and Yan Zhang: These authors contributed equally to this study.

  2. Professor Xun Qu, Institute of Basic Medical Sciences, Qilu Hospital of Shandong University, Jinan 250012, China E-mail: quxun@sdu.edu.cn

Authors and Affiliations

  1. Institute of Basic Medical Sciences, Qilu Hospital of Shandong University, Jinan, China

    Jintang Sun, Yan Zhang, Meixiang Yang, Yun Zhang, Qi Xie, Zewu Li, Zhaogang Dong, Yongmei Yang, Biping Deng, Alei Feng, Weixu Hu, Haiting Mao & Xun Qu

  2. Shandong Center for Disease Control and Prevention, Jinan, China,

    Yan Zhang

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Sun, J., Zhang, Y., Yang, M. et al. Hypoxia induces T-cell apoptosis by inhibiting chemokine C receptor 7 expression: the role of adenosine receptor A2. Cell Mol Immunol 7, 77–82 (2010). https://doi.org/10.1038/cmi.2009.105

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