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Silencing Adenosine A2a Receptor Enhances Dendritic Cell-Based Cancer Immunotherapy Publisher Pubmed



Masjedi A1, 2 ; Ahmadi A3 ; Ghani S4 ; Malakotikhah F5 ; Nabi Afjadi M6 ; Irandoust M7 ; Karoon Kiani F7 ; Heydarzadeh Asl S7 ; Atyabi F8 ; Hassannia H9 ; Hojjatfarsangi M10, 11 ; Namdar A12 ; Ghalamfarsa G13 ; Jadidiniaragh F1, 14
Authors
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Authors Affiliations
  1. 1. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  2. 2. Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
  3. 3. Department of Chemical and Materials Engineering, The University of Alabama in Huntsville, AL, United States
  4. 4. Student Research Committee, Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  5. 5. Department of Clinical Biochemistry, Islamic Azad University, Falavarjan Branch, Isfahan, Iran
  6. 6. Department of Biochemistry, Faculty of Biological Sciences, University of Tarbiat Modares, Tehran, Iran
  7. 7. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  8. 8. Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  9. 9. Immunogenetic Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
  10. 10. Bioclinicum, Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden
  11. 11. The Persian Gulf Marine Biotechnology Medicine Research Center, Bushehr University of Medical Sciences, Bushehr, Iran
  12. 12. Department of Oncology, Cross Cancer Institute, The University of Alberta, Edmonton, AB, Canada
  13. 13. Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran
  14. 14. Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

Source: Nanomedicine: Nanotechnology# Biology# and Medicine Published:2020


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. © 2020 Elsevier Inc.
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