λ-Carrageenan improves the antitumor effect of dendritic cellbased vaccine

Oncotarget. 2017 May 2;8(18):29996-30007. doi: 10.18632/oncotarget.15610.

Abstract

In this study, we investigated the effect of λ-carrageenan on the maturation and function of dendritic cells (DCs) and its adjuvant effect on DC-based vaccine. We found that λ-carrageenan dose-dependently decreased the endocytosis of DCs, promoted DC maturation and increased cytokine production through TLR4 mediated signaling pathway. λ-carrageenan treatment also enhanced the ability of DCs in the stimulating allogenic splenocyte proliferation. In TC-1 tumor mouse model, HPV peptides pulsed λ-carrageenan-DC (HPV-CGN-DC) significantly inhibited tumor growth compared with control group. The frequencies of CD4+ and CD8+ T cells in spleens of tumor mice and their activation status were significantly increased in HPV-CGN-DC group, but the frequencies of natural regulatory T cells and CD11b+Gr-1+ cells were significantly decreased. Further, HPV-CGN-DC induced strong CD8+ T cell responses, which are negatively correlated with tumor volumes. The results suggested that λ-carrageenan promoted DC maturation through TLR4 signaling pathway and could be used as the adjuvant in DC-based vaccines.

Keywords: TLR4; cancer immunotherapy; cellular responses; dendritic cell-based vaccine; λ-carrageenan.

MeSH terms

  • Animals
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / immunology*
  • Carrageenan / pharmacology*
  • Cell Survival / drug effects
  • Combined Modality Therapy
  • Cytokines / metabolism
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Disease Models, Animal
  • Endocytosis / drug effects
  • Endocytosis / immunology
  • Humans
  • Immunotherapy
  • Mice
  • Neoplasms / immunology*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Signal Transduction / drug effects
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Toll-Like Receptor 4 / metabolism
  • Treatment Outcome
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • Cancer Vaccines
  • Cytokines
  • Toll-Like Receptor 4
  • Carrageenan