Oxygen‐Generating Cryogels Restore T Cell Mediated Cytotoxicity in Hypoxic Tumors

Solid tumors are protected from antitumor immune responses due to their hypoxic microenvironments. Weakening hypoxia‐driven immunosuppression by hyperoxic breathing of 60% oxygen has shown to be effective in unleashing antitumor immune cells against solid tumors. However, efficacy of systemic oxygenation is limited against solid tumors outside of lungs and has been associated with unwanted side effects. As a result, it is essential to develop targeted oxygenation alternatives to weaken tumor hypoxia as novel approaches to restore immune responses against cancer. Herein, injectable oxygen‐generating cryogels (O2‐cryogels) to reverse tumor‐induced hypoxia are reported. These macroporous biomaterials are designed to locally deliver oxygen, inhibit the expression of hypoxia‐inducible genes in hypoxic melanoma cells, and reduce the accumulation of immunosuppressive extracellular adenosine. The data show that O2‐cryogels enhance T cell‐mediated secretion of cytotoxic proteins, restoring the killing ability of tumor‐specific cytotoxic T lymphocytes, both in vitro and in vivo. In summary, O2‐cryogels provide a unique and safe platform to supply oxygen as a coadjuvant in hypoxic tumors and have the potential to improve cancer immunotherapies. Injectable oxygen‐generating cryogels (O2‐cryogels) have been leveraged as a strategy to boost antitumor immune responses. These noninvasive biomaterials are designed to controllably release oxygen, reverse hypoxia‐driven immunosuppression, and promote the infiltration of pre‐existing immune‐fighting immune cells into tumors. O2‐cryogels are a novel platform to deliver oxygen locally as a coadjuvant, reinforce tumor‐infiltrating T cells, and ultimately enhance cancer immunotherapies.