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

Tumour Biol. 2017 Mar;39(3):1010428317695021. doi: 10.1177/1010428317695021.

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.

Keywords: Adenosine; CD73; cancer; dendritic cell; immunotherapy.

MeSH terms

  • 5'-Nucleotidase / antagonists & inhibitors*
  • 5'-Nucleotidase / immunology
  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / immunology
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / immunology
  • Breast Neoplasms / pathology
  • Cancer Vaccines / genetics
  • Cancer Vaccines / immunology*
  • Cancer Vaccines / therapeutic use
  • Cell Line, Tumor
  • Cell- and Tissue-Based Therapy
  • Dendritic Cells / immunology
  • Female
  • GPI-Linked Proteins / antagonists & inhibitors
  • GPI-Linked Proteins / immunology
  • Humans
  • Immunity, Innate / drug effects
  • Mice
  • Neoplasms, Experimental / drug therapy*
  • Neoplasms, Experimental / immunology
  • Neoplasms, Experimental / pathology
  • Purinergic P1 Receptor Antagonists / administration & dosage*
  • Receptor, Adenosine A2A / genetics
  • Receptor, Adenosine A2A / immunology*
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / immunology

Substances

  • Antibodies, Monoclonal
  • Cancer Vaccines
  • GPI-Linked Proteins
  • Purinergic P1 Receptor Antagonists
  • Receptor, Adenosine A2A
  • 5'-Nucleotidase
  • NT5E protein, human