Hypoxia: a key player in antitumor immune response. A Review in the Theme: Cellular Responses to Hypoxia

Am J Physiol Cell Physiol. 2015 Nov 1;309(9):C569-79. doi: 10.1152/ajpcell.00207.2015. Epub 2015 Aug 26.


The tumor microenvironment is a complex system, playing an important role in tumor development and progression. Besides cellular stromal components, extracellular matrix fibers, cytokines, and other metabolic mediators are also involved. In this review we outline the potential role of hypoxia, a major feature of most solid tumors, within the tumor microenvironment and how it contributes to immune resistance and immune suppression/tolerance and can be detrimental to antitumor effector cell functions. We also outline how hypoxic stress influences immunosuppressive pathways involving macrophages, myeloid-derived suppressor cells, T regulatory cells, and immune checkpoints and how it may confer tumor resistance. Finally, we discuss how microenvironmental hypoxia poses both obstacles and opportunities for new therapeutic immune interventions.

Keywords: autophagy and antitumor immune response; cancer stem cells; circulating tumor cells; epithelial-mesenchymal transition; hypoxia; hypoxia-inducible factor; immune suppression; lymphoid cells; myeloid cells; programmed death-ligand 1; tumor microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Hypoxia
  • Humans
  • Hypoxia / immunology*
  • Hypoxia / metabolism
  • Hypoxia / pathology
  • Immune Tolerance
  • Immunotherapy / methods
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Macrophages / immunology
  • Macrophages / metabolism
  • Neoplasms / immunology*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Oxygen / metabolism
  • Signal Transduction
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • Tumor Escape*
  • Tumor Microenvironment*


  • Oxygen