Overexpression of adenosine in the tumor region leads to suppression of various immune cells, particularly T cells through ligation with adenosine 2a receptor (A2aR). In this study, we intended to increase the efficacy of tumor lysate-loaded DC vaccine by silencing the expression of A2aR on T cells through the application of A2aR-specific siRNA-loaded PEG-chitosan-lactate (PCL) nanoparticles (NPs) in the 4T1 breast tumor-bearing mice. Combination therapy by DC vaccine and siRNA-loaded NPs markedly induced tumor regression and increased survival time of mice. These ameliorative effects were partly via downregulation of immunosuppressive cells, increased function of cytotoxic T lymphocytes, and induction of immune-stimulatory cytokines. Moreover, combination therapy could markedly suppress angiogenesis and metastasis processes. These results imply the efficacy of novel combination therapy for the treatment of breast cancer by using A2aR siRNA-loaded NPs and DC vaccine which can be translated into the initial phase of clinical trials in the near future.

腺苷在肿瘤区域的过度表达导致各种免疫细胞的抑制，特别是通过与腺苷 2a 受体 (A2aR) 连接的 T 细胞。在这项研究中，我们打算通过在 T 细胞中应用载有 A2aR 特异性 siRNA 的 PEG-壳聚糖乳酸盐 (PCL) 纳米颗粒 (NPs) 来沉默 A2aR 在 T 细胞上的表达，从而提高载有肿瘤裂解物的 DC 疫苗的功效。 4T1 乳腺荷瘤小鼠。DC 疫苗和载有 siRNA 的 NP 的联合疗法显着诱导了肿瘤消退并延长了小鼠的存活时间。这些改善作用部分是通过下调免疫抑制细胞、增加细胞毒性 T 淋巴细胞的功能和诱导免疫刺激细胞因子实现的。此外，联合疗法可以显着抑制血管生成和转移过程。