越来越多的证据证明，肿瘤通过免疫逃逸机制逃避免疫系统的识别和攻击，而PDL1/Pbrm1基因与免疫检查点阻断（ICB）治疗反应不佳或耐药有很强的相关性。在此，我们开发了一种多功能仿生纳米载体（siRNA-CaP@PD1-NVs），它不仅可以通过阻断PD1/PDL1轴增强免疫细胞的细胞毒活性，还可以通过Pbrm1/PDL1基因沉默减少肿瘤免疫逃逸，领先显着改善肿瘤免疫抑制微环境。因此，纳米载体促进DC细胞成熟，增强CD8 T细胞的浸润和活性，形成长期免疫记忆，可以有效抑制肿瘤生长甚至消灭肿瘤，防止肿瘤复发和转移。总体而言，这项研究提出了一种强有力的共同递送 siRNA 药物、免疫佐剂和免疫检查点抑制剂的策略，并为提高当前免疫治疗方案的有效性和安全性带来了巨大希望。© 2024 作者。 《Advanced Science》由 Wiley‐VCH GmbH 出版。

Growing evidences have proved that tumors evade recognition and attack by the immune system through immune escape mechanisms, and PDL1/Pbrm1 genes have a strong correlation with poor response or resistance to immune checkpoint blockade (ICB) therapy. Herein, a multifunctional biomimetic nanocarrier (siRNA-CaP@PD1-NVs) is developed, which can not only enhance the cytotoxic activity of immune cells by blocking PD1/PDL1 axis, but also reduce tumor immune escape via Pbrm1/PDL1 gene silencing, leading to a significant improvement in tumor immunosuppressive microenvironment. Consequently, the nanocarrier promotes DC cell maturation, enhances the infiltration and activity of CD8+ T cells, and forms long-term immune memory, which can effectively inhibit tumor growth or even eliminate tumors, and prevent tumor recurrence and metastasis. Overall, this study presents a powerful strategy for co-delivery of siRNA drugs, immune adjuvant, and immune checkpoint inhibitors, and holds great promise for improving the effectiveness and safety of current immunotherapy regimens.© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.