Enhancement of Immune Checkpoint Inhibitor-Mediated Anti-Cancer Immunity by Intranasal Treatment of Ecklonia cava Fucoidan against Metastatic Lung Cancer

Int J Mol Sci. 2021 Aug 24;22(17):9125. doi: 10.3390/ijms22179125.

Abstract

Although fucoidan, a well-studied seaweed-extracted polysaccharide, has shown immune stimulatory effects that elicit anticancer immunity, mucosal adjuvant effects via intranasal administration have not been studied. In this study, the effect of Ecklonia cava-extracted fucoidan (ECF) on the induction of anti-cancer immunity in the lung was examined by intranasal administration. In C57BL/6 and BALB/c mice, intranasal administration of ECF promoted the activation of dendritic cells (DCs), natural killer (NK) cells, and T cells in the mediastinal lymph node (mLN). The ECF-induced NK and T cell activation was mediated by DCs. In addition, intranasal injection with ECF enhanced the anti-PD-L1 antibody-mediated anti-cancer activities against B16 melanoma and CT-26 carcinoma tumor growth in the lungs, which were required cytotoxic T lymphocytes and NK cells. Thus, these data demonstrated that ECF functioned as a mucosal adjuvant that enhanced the immunotherapeutic effect of immune checkpoint inhibitors against metastatic lung cancer.

Keywords: Ecklonia cava fucoidan; anti-PD-L1 antibody; anti-cancer; immunotherapy; mucosal adjuvant.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / pharmacology
  • Adjuvants, Immunologic / therapeutic use*
  • Administration, Intranasal
  • Animals
  • Cell Line, Tumor
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Drug Combinations
  • Female
  • Immune Checkpoint Inhibitors / administration & dosage
  • Immune Checkpoint Inhibitors / therapeutic use*
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology
  • Laminaria / chemistry*
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Neoplasm Metastasis
  • Plant Extracts
  • Polysaccharides / administration & dosage
  • Polysaccharides / pharmacology
  • Polysaccharides / therapeutic use*

Substances

  • Adjuvants, Immunologic
  • Drug Combinations
  • Immune Checkpoint Inhibitors
  • Plant Extracts
  • Polysaccharides
  • fucoidan