Hypoxia Induces T-cell Apoptosis by Inhibiting Chemokine C Receptor 7 Expression: The Role of Adenosine Receptor A(2)

Cell Mol Immunol. 2010 Jan;7(1):77-82. doi: 10.1038/cmi.2009.105. Epub 2009 Dec 23.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Cell Hypoxia
  • Cells, Cultured
  • Gene Expression Regulation
  • Humans
  • Receptor, Adenosine A2A / genetics
  • Receptor, Adenosine A2A / immunology
  • Receptor, Adenosine A2A / metabolism*
  • Receptor, Adenosine A2B / genetics
  • Receptor, Adenosine A2B / immunology
  • Receptor, Adenosine A2B / metabolism*
  • Receptors, CCR7 / immunology*
  • Signal Transduction
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism

Substances

  • CCR7 protein, human
  • Receptor, Adenosine A2A
  • Receptor, Adenosine A2B
  • Receptors, CCR7