Silencing adenosine A2a receptor enhances dendritic cell-based cancer immunotherapy
Silencing adenosine A2a receptor enhances dendritic cell-based cancer immunotherapy
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DOI：
10.1016/j.nano.2020.102240
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发表时间：
2020-10-01
影响因子：
5.4
通讯作者：
Jadidi-Niaragh, Farhad
中科院分区：
文献类型：
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作者：
Masjedi, Ali;Ahmadi, Armin;Jadidi-Niaragh, Farhad
腺苷在肿瘤区域的过度表达通过与腺苷2a受体（A2aR）的结扎导致多种免疫细胞，特别是T细胞的抑制。在这项研究中，我们打算通过在4T1乳腺荷瘤小鼠中应用负载A2aR特异性sirna的peg -壳聚糖乳酸（PCL）纳米颗粒（NPs）来沉默T细胞上A2aR的表达，从而提高负载肿瘤裂解物的DC疫苗的功效。DC疫苗与负载sirna的NPs联合治疗可显著诱导肿瘤消退，延长小鼠生存时间。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。此外，联合治疗可明显抑制血管生成和转移过程。这些结果表明，利用装载A2aR sirna的NPs和DC疫苗联合治疗乳腺癌的新型联合疗法在不久的将来可以进入临床试验的初始阶段。(C) 2020爱思唯尔公司版权所有。
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. (C) 2020 Elsevier Inc. All rights reserved.