Mechanisms of HIF-driven immunosuppression in tumour microenvironment

Hypoxia arises due to insufficient oxygen delivery to rapidly proliferating tumour cells that outpace the available blood supply. It is a characteristic feature of most solid tumour microenvironments and plays a critical role in regulating anti-tumour immunity, enhancing tumoral heterogeneity, and promoting therapeutic resistance and poor clinical outcomes. Hypoxia-inducible factors (HIFs) are the major hypoxia-responsive transcription factors that are activated under low oxygenation conditions and have been identified to drive multifunctional roles in tumour immune evasion. The HIF signalling network serves as an attractive target for targeted therapeutic approaches. This review aims to provide a comprehensive overview of the most crucial mechanisms by which HIF controls the expression of immunosuppressive molecules and immune checkpoints, disrupts cancer immunogenicity, and induces immunotherapeutic resistance.