Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Chemical and Materials Engineering, The University of Alabama in Huntsville, AL, USA.
Nanomedicine. 2020 Oct;29:102240. doi: 10.1016/j.nano.2020.102240. Epub 2020 Jun 15.
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.
肿瘤部位的腺苷过表达通过与腺苷 2a 受体（A2aR）的结合导致各种免疫细胞，特别是 T 细胞的抑制。在这项研究中，我们旨在通过在 4T1 乳腺癌荷瘤小鼠中应用载有 A2aR 特异性 siRNA 的聚乙二醇-壳聚糖-乳酸（PCL）纳米颗粒（NPs）沉默 T 细胞上的 A2aR 表达，来提高肿瘤裂解物负载的 DC 疫苗的疗效。DC 疫苗和载有 siRNA 的 NPs 的联合治疗显著诱导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来实现的。此外，联合治疗还可以显著抑制血管生成和转移过程。这些结果表明，使用载有 A2aR siRNA 的 NPs 和 DC 疫苗的新型联合治疗方法对乳腺癌的治疗具有疗效，该方法有望在不久的将来转化为临床试验的初期阶段。
