Figure 1.

The hypoxic tumour microenvironment (TME). Hypoxia plays an important role in the development of the TME. The TME is composed of hypoxic tumour cells, cancer stem cells, tumour cells, immune cells, cytokines/chemokines, collagen, fibronectin, cancer associated fibroblasts (CAFs), endothelial cells and, blood vessels. As the tumour cells grow, the tumour cells further away from the blood supply have limited access to oxygen and become hypoxic tumour cells. Additionally, the TME undergoes a metabolic switch to meet the demands of the TME which involves increased glucose uptake and production of lactate resulting in an acidic TME characterised by a decreasing pH. These changes result in a change in cytokine/chemokine release, a change in immune cell phenotype, modification of the extracellular matrix, and activation of CAFs. Together, these form a more pro-tumorigenic environment prone to increased invasive and metastatic potential, as well as increased resistance to chemoradiotherapy. Created with BioRender.com.