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Oxygen-Generating Cryogels Restore T Cell Mediated Cytotoxicity in Hypoxic Tumors.

ABSTRACT: 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, we report on injectable oxygen-generating cryogels (O₂-cryogels) to reverse tumor-induced hypoxia. These macroporous biomaterials were designed to locally deliver oxygen, inhibit the expression of hypoxia-inducible genes in hypoxic melanoma cells, and reduce the accumulation of immunosuppressive extracellular adenosine. Our data show that O₂-cryogels enhance T cell-mediated secretion of cytotoxic proteins, restoring the killing ability of tumor-specific CTLs, both in vitro and in vivo. In summary, O₂-cryogels provide a unique and safe platform to supply oxygen as a co-adjuvant in hypoxic tumors and have the potential to improve cancer immunotherapies.

SUBMITTER: Colombani T

PROVIDER: S-EPMC10516343 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Oxygen-Generating Cryogels Restore T Cell Mediated Cytotoxicity in Hypoxic Tumors.

Colombani Thibault T Eggermont Loek J LJ Hatfield Stephen M SM Rogers Zachary J ZJ Rezaeeyazdi Mahboobeh M Memic Adnan A Sitkovsky Michail V MV Bencherif Sidi A SA

Advanced functional materials 20210623 37

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 hyp ...[more]

PMID: 37745940

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Project description:Provision of supplemental oxygen to maintain soft tissue viability acutely following trauma in which vascularization has been compromised would be beneficial for limb and tissue salvage. For this application, an oxygen generating biomaterial that may be injected directly into the soft tissue could provide an unprecedented treatment in the acute trauma setting. The purpose of the current investigation was to determine if sodium percarbonate (SPO), an oxygen generating biomaterial, is capable of maintaining resting skeletal muscle homeostasis under otherwise hypoxic conditions. In the current studies, a biologically and physiologically compatible range of SPO (1-2 mg/mL) was shown to: 1) improve the maintenance of contractility and attenuate the accumulation of HIF1?, depletion of intramuscular glycogen, and oxidative stress (lipid peroxidation) that occurred following ?30 minutes of hypoxia in primarily resting (duty cycle?=?0.2 s train/120 s contraction interval <0.002) rat extensor digitorum longus (EDL) muscles in vitro (95% N2-5% CO2, 37°C); 2) attenuate elevations of rat EDL muscle resting tension that occurred during contractile fatigue testing (3 bouts of 25 100 Hz tetanic contractions; duty cycle?=?0.2 s/2 s?=?0.1) under oxygenated conditions in vitro (95% O2-5% CO2, 37°C); and 3) improve the maintenance of contractility (in vivo) and prevent glycogen depletion in rat tibialis anterior (TA) muscle in a hindlimb ischemia model (i.e., ligation of the iliac artery). Additionally, injection of a commercially available lipid oxygen-carrying compound or the components (sodium bicarbonate and hydrogen peroxide) of 1 mg/mL SPO did not improve EDL muscle contractility under hypoxic conditions in vitro. Collectively, these findings demonstrate that a biological and physiological concentration of SPO (1-2 mg/mL) injected directly into rat skeletal muscle (EDL or TA muscles) can partially preserve resting skeletal muscle homeostasis under hypoxic conditions.

Dataset Information

Oxygen-Generating Cryogels Restore T Cell Mediated Cytotoxicity in Hypoxic Tumors.

Publications

Oxygen-Generating Cryogels Restore T Cell Mediated Cytotoxicity in Hypoxic Tumors.

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