Hypoxic areas in the tumour are typically devoid of effector T cells but enriched in pro-angiogenic, immunosuppressive TAMs and Tregs.63, 64, 65, 66 Hypoxia is one of the key drivers of immune tolerance in the TME, which promotes immunoregulatory cell phenotypes,64,65 up-regulates the expression of immune checkpoints and other inhibitory molecules, like transforming growth factor-β (TGF-β) and adenosine.63 This evidence concerns the gene TGFB1 and neoplasm.