title: Hypoxia induces T-cell apoptosis by inhibiting chemokine C receptor 7 expression: the role of adenosine receptor A(2).
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 A(2a )and A(2b) 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 A(2)R 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 A(2)R signaling pathway partly by suppressing CCR7. Blocking the A(2)R 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.
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital of Shandong University, Jinan, China.
authors.forename: Jintang
authors.initials: J
authors.lastname: Sun
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Meixiang
authors.initials: M
authors.lastname: Yang
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Qi
authors.initials: Q
authors.lastname: Xie
authors.forename: Zewu
authors.initials: Z
authors.lastname: Li
authors.forename: Zhaogang
authors.initials: Z
authors.lastname: Dong
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Yang
authors.forename: Biping
authors.initials: B
authors.lastname: Deng
authors.forename: Alei
authors.initials: A
authors.lastname: Feng
authors.forename: Weixu
authors.initials: W
authors.lastname: Hu
authors.forename: Haiting
authors.initials: H
authors.lastname: Mao
authors.forename: Xun
authors.initials: X
authors.lastname: Qu
mesh_terms: D017209:Apoptosis; D015687:Cell Hypoxia; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D043705:Receptor, Adenosine A2A / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D043704:Receptor, Adenosine A2B / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D054400:Receptors, CCR7 / Q000276:immunology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
chemical_list: C515370:CCR7 protein, human; D043705:Receptor, Adenosine A2A; D043704:Receptor, Adenosine A2B; D054400:Receptors, CCR7