Dendritic Cell-Based Vaccines Positively Impact Natural Killer and Regulatory T Cells in Hepatocellular Carcinoma Patients

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Abstract
Immunotherapy of cancer must promote antitumor effector cells for tumor eradication as well as counteract immunoregulatory mechanisms which inhibit effectors. Immunologic therapies of cancer are showing promise, including dendritic cell-(DC-) based strategies. DC are highly malleable antigen-presenting cells which can promote potent antitumor immunity as well as tolerance, depending on the environmental signals received. Previously, we tested a peptide-pulsed DC vaccine to promote Alpha-fetoprotein (AFP-) specific anti-tumor immunity in patients with hepatocellular carcinoma (HCC), and reported on the CD8+T cell responses induced by this vaccine and the clinical trial results. Here, we show that the peptide-loaded DC enhanced NK cell activation and decreased regulatory T cells (Treg) frequencies in vaccinated HCC patients. We also extend these data by testing several forms of DC vaccinesin vitroto determine the impact of antigen loading and maturation signals on both NK cells and Treg from healthy donors and HCC patients.
Funding Information
  • University of Pittsburgh (T35 DK065521 T, RO1 CA 104524)
  • National Institute of Diabetes and Digestive and Kidney Diseases (T35 DK065521 T, RO1 CA 104524)
  • National Cancer Institute (T35 DK065521 T, RO1 CA 104524)

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