Abstract 5848: Oxygen-releasing cryogel reinforce dendritic cell function and T-cell mediated tumor immunity in hypoxic microenvironments

Cancer immunotherapy faces significant barriers due to tumor heterogeneity and the hypoxic nature of the solid tumor microenvironment (TME). Hypoxia, defined by reduced oxygen (O2) tension, induces immunosuppression, impairing dendritic cell (DC) and T-cell function, which are critical for robust anti-tumor immunity. Here, we report on the evaluation of a novel hyaluronic acid (HA)-based cryogel scaffold, termed O2-cryogels, engineered to counteract hypoxia by releasing O2 through encapsulated calcium peroxide (CaO2) particles and catalase enzyme. Our results demonstrate that O2-cryogels effectively alleviate hypoxia-induced suppression of murine and human DC function. Specifically, they rescue critical DC processes such as antigen uptake, migratory activity, and the expression of activation and co-stimulatory molecules essential for T-cell priming. Moreover, O2-cryogels enhance the secretion of proinflammatory cytokines, mitigate hypoxia-induced phenotypic switching of mouse DCs to tolerogenic plasmacytoid DCs (pDCs), and suppress the upregulation of hypoxia-induced tolerance markers. These effects translate to restored allogenic T-cell proliferation and improved OT-I cell-mediated cytotoxicity against B16-OVA tumor cells under hypoxic conditions. This study highlights the ability of O2-cryogels to locally modulate oxygen levels, reinvigorate DC function, and enhance T-cell-mediated tumor cell killing, addressing a critical bottleneck in cancer immunotherapy. By targeting hypoxia, O2-cryogels offer a novel and promising approach to amplify the efficacy of immunotherapeutic strategies, paving the way for innovative treatments in hypoxia-driven solid tumors. Citation Format: Khushbu Bhatt. Oxygen-releasing cryogel reinforce dendritic cell function and T-cell mediated tumor immunity in hypoxic microenvironments [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5848.