Table 1.
Influence of hypoxia on TME components
| TME component | Influence of hypoxic environment | Cancer suppression (+)/promotion (−) |
|---|---|---|
| CAF progenitors | Recruitment, activation and transformation into CAFs | − |
| CAFs | Secretion of cytokines, promoting tumour growth | − |
| Deactivation by chronic hypoxia | + | |
| ECM | Increase of ECM deposition (fibrosis) and remodelling | − |
| Increase of interaction with cancer cells | − | |
| Blood vessels | Increase in vascularisation by HIF-1 | − |
| Decrease in vascularisation by HIF-2 | + | |
| Lymphatic vessels | Increase in lymphangiogenesis by HIF-1 | − |
| Decrease in lymphangiogenesis by HIF-2 | ? | |
| Neutrophils | Recruitment to tumour | ? |
| Increase in survival and function | ? | |
| Macrophage | Maturation and functioning are dependent on HIF1 | ? |
| Recruitment from bloodflow | − | |
| Increase in migratory capacity | − | |
| M2 polarisation | − | |
| MDSCs | Enhancement of immune-suppressive function | − |
| Polarisation to M1 type, driven by SIRT1 | + | |
| Non-specific CD4+ cells | Differentiation into regulatory T-cells and T-helpers | −/? |
| Regulatory T-cells | Recruitment from bloodflow | − |
| Enhancement of immune suppressive function | − | |
| Effector T-cells | Immune checkpoints activation | − |
| Repression due to “metabolic competition” for nutrients | − | |
| CD8+ T-cells | Support in proliferation, differentiation and activation | + |