Increased efficacy of a dendritic cell–based therapeutic cancer vaccine with adenosine receptor antagonist and CD73 inhibitor

Author:

Arab Samaneh1,Kheshtchin Nasim2,Ajami Maryam3,Ashurpoor Mahbubeh4,Safvati Aida2,Namdar Afshin2,Mirzaei Reza2,Mousavi Niri Neda5,Jadidi-Niaragh Farhad467,Ghahremani Mohammad Hossein1,Hadjati Jamshid2

Affiliation:

1. Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran

2. Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

3. Department of Immunology, Tarbiat Modares University, Tehran, Iran

4. Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

5. Department of Biotechnology, Faculty of Advanced Medical Sciences, Tehran Medical Branch, Islamic Azad University, Tehran, Iran

6. Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

7. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

Abstract

Dendritic cells are important in initiating immune responses; therefore, a range of dendritic cell–based approaches have been established to induce immune response against cancer cells. However, the presence of immunosuppressive mediators such as adenosine in the tumor microenvironment reduces the efficacy of dendritic cell–based cancer immunotherapy. In this study, we investigated whether blockade of the A2A adenosine receptor with a selective antagonist and a CD73 inhibitor may increase the efficacy of a dendritic cell–based cancer vaccine. According to the findings, this therapeutic combination reduced tumor growth, prolonged survival of tumor-bearing mice, and enhanced specific antitumor immune responses. Thus, we suggest that targeting cancer-derived adenosine improves the outcomes of dendritic cell–based cancer immunotherapy.

Publisher

IOS Press

Subject

General Medicine

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