Intranasal Administration of Codium fragile Polysaccharide Elicits Anti-Cancer Immunity against Lewis Lung Carcinoma

Int J Mol Sci. 2021 Sep 30;22(19):10608. doi: 10.3390/ijms221910608.

Abstract

Natural polysaccharides have shown promising effects on the regulation of immunity in animals. In this study, we examined the immune stimulatory effect of intranasally administered Codium fragile polysaccharides (CFPs) in mice. Intranasal administration of CFPs in C57BL/6 mice induced the upregulation of surface activation marker expression in macrophages and dendritic cells (DCs) in the mediastinal lymph node (mLN) and the production of interleukin-6 (IL-6), IL-12p70, and tumor necrosis factor-α in bronchoalveolar lavage fluid. Moreover, the number of conventional DCs (cDCs) was increased in the mLNs by the upregulation of C-C motif chemokine receptor 7 expression, and subsets of cDCs were also activated following the intranasal administration of CFP. In addition, the intranasal administration of CFPs promoted the activation of natural killer (NK) and T cells in the mLNs, which produce pro-inflammatory cytokines and cytotoxic mediators. Finally, daily administration of CFPs inhibited the infiltration of Lewis lung carcinoma cells into the lungs, and the preventive effect of CFPs on tumor growth required NK and CD8 T cells. Furthermore, CFPs combined with anti-programmed cell death-ligand 1 (PD-L1) antibody (Ab) improved the therapeutic effect of anti-PD-L1 Ab against lung cancer. Therefore, these data demonstrated that the intranasal administration of CFP induced mucosal immunity against lung cancer.

Keywords: Codium fragile polysaccharide; Lewis lung carcinoma; anti-cancer; immunotherapy; mucosal adjuvant.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Administration, Intranasal / methods
  • Animals
  • Antineoplastic Agents / administration & dosage*
  • CD8-Positive T-Lymphocytes / immunology
  • Carcinoma, Lewis Lung / immunology*
  • Carcinoma, Lewis Lung / pathology
  • Carcinoma, Lewis Lung / therapy*
  • Cell Line, Tumor
  • Chlorophyta / chemistry*
  • Dendritic Cells / immunology
  • Disease Models, Animal
  • Female
  • Immunity, Mucosal*
  • Immunotherapy / methods*
  • Killer Cells, Natural / immunology
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy*
  • Lymphocyte Activation / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Phytotherapy / methods*
  • Plant Extracts / administration & dosage*
  • Polysaccharides / administration & dosage*

Substances

  • Adjuvants, Immunologic
  • Antineoplastic Agents
  • Plant Extracts
  • Polysaccharides