Inhibition of apelin/APJ axis enhances the potential of dendritic cell-based vaccination to modulate TH1 and TH2 cell-related immune responses in an animal model of metastatic breast cancer.

Autor: Masoumi J; Department of Immunology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran; Molecular Medicine Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran., Jafarzadeh A; Department of Immunology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran; Molecular Medicine Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran; Department of Immunology, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran. Electronic address: Jafarzadeh14@yahoo.com., Tavakoli T; Department of Immunology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran., Basirjafar P; Department of Immunology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran., Zandvakili R; Department of Immunology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran., Javan MR; Department of Immunology, Faculty of Medicine, Zabol University of Medical Sciences, Zabol, Iran., Taghipour Z; Department of Anatomy, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran., Moazzeni SM; Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Jazyk: angličtina
Zdroj: Advances in medical sciences [Adv Med Sci] 2022 Mar; Vol. 67 (1), pp. 170-178. Date of Electronic Publication: 2022 Mar 12.
DOI: 10.1016/j.advms.2022.02.006
Abstrakt: Purpose: The immunosuppressive microenvironment of tumors reduces the effectiveness of immunotherapies. Apelin as an immunosuppressor peptide is expressed in the microenvironment of many tumors. Thus, inhibition of apelin-related protumor activities can promote the effectiveness of cancer immunotherapy. Here, we investigated the efficacy of a dendritic cell (DC) vaccine in combination with an apelin receptor antagonist, ML221, to modulate Th1 and Th2 cell-related responses in breast cancer-bearing mice.
Materials and Methods: Tumor was induced in female BALB/c mice by injecting 7 ​× ​10 5 4T1 cells in the right flank. Tumor-bearing mice were then given PBS, ML221, DC vaccine and "ML221 + DC vaccine" for 21 days. On day 37, mice were sacrificed and the frequency of Th1/Th2 cells in spleen and serum levels of IFN-γ/IL-10 were determined using flow cytometry and ELISA, respectively. Lung metastasis was evaluated in lung tissues stained with hematoxylin and eosin. Finally, the obtained data were analyzed using appropriate statistical tests.
Results: Combination therapy with ML221 + DC vaccination was more effective in reducing tumor growth (P ​< ​0.0001), preventing lung metastasis (P ​< ​0.0001) and increasing survival rate (P ​< ​0.01) compared to the control group. Moreover, combination treatment substantially increased the frequency of Th1 cells while decreasing the frequency of Th2 cells in the spleen compared to the control group (P ​< ​0.01). It also reduced serum levels of IL-10 compared with the control group (P ​< ​0.05).
Conclusion: Our findings showed that combination therapy using ML221 + DC vaccine can be considered as an effective cancer therapeutic program to potentiate anti-tumor immune responses.
Competing Interests: Declaration of competing interest The authors declare no conflict of interest.
(Copyright © 2022 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: