Silencing adenosine A2a receptor enhances dendritic cell-based cancer immunotherapy

Autor: Mohammad Hojjat-Farsangi, Fatemeh Atyabi, Ali Masjedi, Mohsen Nabi Afjadi, Fariba Karoon Kiani, Farinaz Malakotikhah, Sima Heydarzadeh Asl, Ghasem Ghalamfarsa, Hadi Hassannia, Farhad Jadidi-Niaragh, Afshin Namdar, Mahzad Irandoust, Sepideh Ghani, Armin Ahmadi
Rok vydání: 2020
Předmět:
Receptor
Adenosine A2A
Angiogenesis
medicine.medical_treatment
Biomedical Engineering
Pharmaceutical Science
Medicine (miscellaneous)
Adenosine A2A receptor
Breast Neoplasms
Mammary Neoplasms
Animal
Bioengineering
02 engineering and technology
CD8-Positive T-Lymphocytes
Cancer Vaccines
Polyethylene Glycols
Metastasis
Mice
03 medical and health sciences
Immune system
Cancer immunotherapy
Cell Line
Tumor
medicine
Animals
Humans
Cytotoxic T cell
General Materials Science
Lactic Acid
RNA
Small Interfering
030304 developmental biology
Chitosan
0303 health sciences
Chemistry
Dendritic Cells
Dendritic cell
021001 nanoscience & nanotechnology
medicine.disease
Adenosine
Adenosine A2 Receptor Antagonists
Gene Expression Regulation
Neoplastic
Disease Models
Animal
Cancer research
Nanoparticles
Molecular Medicine
Female
Immunotherapy
0210 nano-technology
T-Lymphocytes
Cytotoxic
medicine.drug
Zdroj: Nanomedicine: Nanotechnology, Biology and Medicine. 29:102240
ISSN: 1549-9634
DOI: 10.1016/j.nano.2020.102240
Popis: 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.
Databáze: OpenAIRE
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