In situ vaccination can trigger an antitumor immune response. However, the therapeutic effect is still limited since the high expression of adenosine binding to G protein-coupled receptor A2AR induces an immunosuppressive effect. In this work, a new formulation is presented with the combination of a nanovaccine based on redox-responsive polymer micelles and A2AR antagonist SCH58261. The micelles simultaneously encapsulate immunogenic cell death (ICD) inducer doxorubicin (DOX) and adjuvant toll-like receptor 7 and 8 (TLR7/8) agonist R848, acting as the potent in situ vaccines. A high concentration of glutathione in tumor cells leads to the disintegration of these micelles, releasing DOX and R848 to mediate ICD, inducing the activation of dendritic cells and initiating an immune response. Meanwhile, A2AR antagonist SCH58261, a generation immune checkpoint blocker, inhibits the immunosuppressive adenosinergic pathway in the tumor microenvironment, activating natural killer (NK) cells and CD8⁺ T cells, and inhibiting the proliferation of regulatory T cells. Therefore, this formulation can trigger a robust systemic antitumor immune response.

中文翻译：

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一种氧化还原反应性纳米疫苗与 A2A 受体拮抗剂联合用于癌症免疫治疗

原位疫苗接种可以引发抗肿瘤免疫反应。然而，由于与 G 蛋白偶联受体 A2AR 结合的腺苷的高表达诱导免疫抑制作用，因此治疗效果仍然有限。在这项工作中，提出了一种新的配方，它结合了基于氧化还原响应性聚合物胶束和 A2AR 拮抗剂 SCH58261 的纳米疫苗。胶束同时封装免疫原性细胞死亡 (ICD) 诱导剂阿霉素 (DOX) 和佐剂 toll 样受体 7 和 8 (TLR7/8) 激动剂 R848，作为有效的原位疫苗。肿瘤细胞中高浓度的谷胱甘肽导致这些胶束解体，释放 DOX 和 R848 介导 ICD，诱导树突状细胞活化并引发免疫反应。同时，A2AR 拮抗剂 SCH58261，⁺ T 细胞，并抑制调节性 T 细胞的增殖。因此，这种配方可以引发强大的全身抗肿瘤免疫反应。