Silencing adenosine A2a receptor enhances dendritic cell-based cancer immunotherapy

Masjedi, A and Ahmadi, A and Ghani, S and Malakotikhah, F and Nabi Afjadi, M and Irandoust, M and Karoon Kiani, F and Heydarzadeh Asl, S and Atyabi, F and Hassannia, H and Hojjat-Farsangi, M and Namdar, A. and Ghalamfarsa, G and Jadidi-Niaragh, F (2020) Silencing adenosine A2a receptor enhances dendritic cell-based cancer immunotherapy. Nanomedicine: Nanotechnology, Biology, and Medicine, 29. ISSN 15499634

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Abstract

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.

Item Type: Article
Uncontrolled Keywords: (A2a) )RAdenosine) (Breast cancer) (Dendritic cell vaccineN) (anoparticle) (siRNA)
Subjects: QW Microbiology and Immunology
Divisions: Faculty of Medicin > Department of Immunology and Allergy
Depositing User: خدیجه شبانکاره
Date Deposited: 26 Dec 2020 10:21
Last Modified: 26 Dec 2020 10:21
URI: http://eprints.bpums.ac.ir/id/eprint/9096

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