Breaking hypoxic barrier: Oxygen-supplied nanomaterials for enhanced T cell-mediated tumor immunotherapy

Abstract

Hypoxia in the tumor microenvironment (TME) is a critical barrier to effective cancer immunotherapy, as it suppresses T cell infiltration and response while fostering immune evasion. Oxygen-supplied nanomaterials (OSNs) have recently emerged as promising tools to alleviate hypoxia, modulate the TME, and enhance the efficacy of immunotherapies. This review explores the synergistic interplay between OSNs and T lymphocytes in overcoming hypoxia-driven immune suppression. We discuss the mechanisms by which hypoxia limits T cell functionality, infiltration, and cytotoxicity, and highlight how nanomaterials restore oxygenation, boost immune activation, and improve chemokine-mediated T cell recruitment. Key advances in nanotechnology, including perfluorocarbon-based systems and catalytic nanoparticles, are evaluated for their ability to improve anti-tumor immunity and synergize with immune checkpoint inhibitors and chimeric antigen receptor-T cell therapies. Finally, we address the challenges of nanomaterial delivery, safety, and clinical translation, emphasizing opportunities for personalized strategies. OSNs offer transformative potential to enhance T cell-mediated anti-tumor responses, advancing immunotherapy's frontier.