Hypoxic tumor microenvironment and immune cell dynamics: From metabolic reprogramming to therapeutic innovation

The tumor microenvironment (TME) comprises the cellular and non-cellular components present within and around a tumor and plays a critical role in tumor progression and development. Metabolic changes in immune cells within the TME have been reported, including alterations of glycolysis, oxidative phosphorylation, and fatty acid oxidation pathways that contribute to tumorigenesis. In the present review, we highlight the significant role of hypoxia within the TME as a primary characteristic of most solid tumors. A comprehensive search of the EMBASE, MEDLINE, and Web of Science databases was conducted, encompassing all literature published up to and including June 2025. This study emphasizes the critical role of hypoxia in the TME and its impact on immune cell function. By understanding how hypoxia affects immune cell metabolism, researchers can develop therapeutic approaches targeting immune cell metabolism in the TME. In this regard, we discussed the role of targeting hypoxia via HIF-1 for immunotherapeutic implications; targeting HIF-1 for immunotherapeutic purposes is an area of active research and holds promise for developing new and more effective cancer treatments.