TGFB1 and neoplasm: Hypoxia may also upregulate PD-1, CTLA-4 and TGF-β expression on the surface of T cells through the adenosine (Ado-A2aR) pathway which further promotes immune tolerance by diverting the cytokine and cellular profile of the TME away from cytotoxic T cell inflammation, leading to tumor progression and metastasis 125.