Abstract Immunotherapy is an ascendant approach in cancer treatment. It shows more pronounced effects on killing cancer cells in a specific manner in particular against metastasis more than traditional techniques, such as chemotherapy or surgery. However, tumor immunosuppression limits the response of the immune system to cancer development. In this study, we developed a lipid-based nanocarrier doubly loaded with imiquimod (R837), a toll-like receptor 7 agonist, and caffeine, an adenosine receptor antagonist. This R837/caffeine loaded nanocarrier served as a nano-immunomodulator (RC-nIM) for combination treatment with radiotherapy (RT) against orthotopic breast cancer. RT-induced immunogenic cell death facilitated the production of tumor antigen and elicited the immune response in corporation with R837-medaited activation of antigen-presenting cells (APCs) while RC-nIMs being adopted. Additionally, caffeine, an adenosine analog, can successfully compete with adenosine in the tumor. The tumor-bearing mice that received RT together with RC-nIMs experienced the best antitumor effects and exhibited higher levels of T cells and APCs within the tumor; the growth of secondary tumors was also limited. This work serves as a proof-of-concept study for the development of a new immunotherapy strategy against cancer.

中文翻译：

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开发封装 R837 和咖啡因的纳米免疫调节剂，用于联合放疗/免疫治疗原位乳腺癌

摘要 免疫治疗是癌症治疗的一种新兴方法。与化学疗法或手术等传统技术相比，它在以特定方式杀死癌细胞尤其是针对转移方面显示出更显着的效果。然而，肿瘤免疫抑制限制了免疫系统对癌症发展的反应。在这项研究中，我们开发了一种基于脂质的纳米载体，双载咪喹莫特 (R837)（一种 Toll 样受体 7 激动剂）和咖啡因（一种腺苷受体拮抗剂）。这种载有 R837/咖啡因的纳米载体作为纳米免疫调节剂 (RC-nIM) 与放疗 (RT) 联合治疗原位乳腺癌。RT 诱导的免疫原性细胞死亡促进了肿瘤抗原的产生，并在采用 RC-nIM 时与 R837 介导的抗原呈递细胞 (APC) 激活一起引发了免疫反应。此外，咖啡因，一种腺苷类似物，可以成功地与肿瘤中的腺苷竞争。接受放疗和 RC-nIM 的荷瘤小鼠抗肿瘤效果最好，肿瘤内 T 细胞和 APC 水平更高；继发性肿瘤的生长也受到限制。这项工作可作为开发针对癌症的新免疫治疗策略的概念验证研究。接受放疗和 RC-nIM 的荷瘤小鼠抗肿瘤效果最好，肿瘤内 T 细胞和 APC 水平更高；继发性肿瘤的生长也受到限制。这项工作可作为开发针对癌症的新免疫治疗策略的概念验证研究。接受放疗和 RC-nIM 的荷瘤小鼠抗肿瘤效果最好，肿瘤内 T 细胞和 APC 水平更高；继发性肿瘤的生长也受到限制。这项工作可作为开发针对癌症的新免疫治疗策略的概念验证研究。