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. Therefore, it is essential to develop targeted oxygenation alternatives to weaken tumor hypoxia as novel approaches to cancer immunotherapies. 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. 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 improve cancer immunotherapies.

中文翻译：

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缺氧肿瘤修复缺氧肿瘤中T细胞介导的细胞毒性

实体瘤因其低氧微环境而免受抗肿瘤免疫反应的影响。通过高氧呼吸60％的氧气来减弱由缺氧引起的免疫抑制作用，可以有效释放针对实体瘤的抗肿瘤免疫细胞。但是，全身性充氧的功效仅限于针对肺外的实体瘤。因此，作为癌症免疫疗法的新方法，开发靶向氧合作用以减弱肿瘤缺氧至关重要。在此，我们报道了可注射的氧气产生冰凝胶（O2-cryogels），以扭转肿瘤引起的缺氧。这些大孔生物材料旨在局部输送氧气，抑制缺氧性黑色素瘤细胞中缺氧诱导基因的表达，并减少免疫抑制性细胞外腺苷的积累。O2-cryogels增强T细胞介导的细胞毒性蛋白的分泌，从而在体外和体内恢复肿瘤特异性CTL的杀伤能力。总之，O2-cryogels提供了一个独特且安全的平台，可在缺氧肿瘤中提供氧气作为辅助佐剂，并改善癌症的免疫疗法。