Hypoxia and immunometabolism in the tumor microenvironment: insights into mechanisms and therapeutic potential

The tumor microenvironment (TME), regulated by both intrinsic oncogenic factors and immune metabolic processes, has become an increasing focus of research in recent years. Typical features of the TME include hypoxia, metabolic dysregulation, and immunosuppression. Metabolic reprogramming provides tumors with energy and biosynthetic compounds to meet the nutritional requirements for proliferation. Meanwhile, immune metabolism influences tumor cells to shape the tumor immunosuppressive microenvironment by altering immune cell function and phenotype. Tumor hypoxia signaling specifically fosters the development of immunosuppressive TME by regulating immune metabolism, which, in turn, supports the progression of malignant tumors through modulation of their biological behaviors. This review comprehensively explores the metabolic regulation of hypoxia and immune metabolism during the dynamic evolution of tumor-adapted TME. In the context of the intricate interplay between hypoxia and immunometabolism, the prospects and challenges associated with immunometabolism in the clinical management of tumors are systematically addressed.