Fig. 1

Hypoxia within TME influences tumor-immune interactions. Despite HIF-1α being generated under normal conditions, available oxygen through the effect of prolyl hydroxylase helps to degrade it ubiquitously without any detrimental downstream effects: immune participants such as NK and T cells can effectively eliminate rapidly proliferating tumor cells. When this oxygen source is deprived, as commonly seen in tumor hypoxia, degradation of HIF-1α is inhibited, leading to the translocation of HIF-1α to inside the nucleus and a cascade of events that involves the binding of HIF-1α and HIF-1β heterodimers to hypoxia-responsive elements (HREs) on DNA. The outcomes of these processes eventually impact hypoxia-responsive outcomes like incidence of pro-tumor immunosuppressant MDSCs, Tregs, and TAMs. These immunosuppressive entities adapt to the oxygen-deprived conditions and compete with T/NK cells for glycolysis and decrease functional efficacy of T cells and NK cells. The collective influence of these events results in modified cell metabolism, enhanced angiogenesis, and increased tumor proliferation and drug resistance