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

Wei Zhang,Peter Chang-Whan Lee,Jun-O Jin,Eun-Koung An,Minseok Kwak,Juyoung Hwang,Dhananjay Yadav

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.

Highlights

Our group has shown that extracted fucoidan (ECF) contained a higher amount of fucose, galactose and sulfate ester group than Macrocystis pyrifera fucodian, Undaria pinnatifida fucoidan and Fucus vesiculosus fucoidan [18] and it promotes the strongest effect of immune cell activation compared to those fucoidans in human peripheral blood mononuclear cells [20]
Since the i.n. administration of ECF promoted dendritic cells (DCs) activation in mediastinal lymph node (mLN), we examined whether the ECF can promote the DC activation in BALB/c mice
We found that i.n. administration of ECF induced immune cell activation including DCs, natural killer (NK) cells, and T cells in the mLN

Summary

Introduction

Sulfated polysaccharides, such as fucoidan, carrageenan, ascophyllan, porphyran, and ulvan have been explored as vaccine adjuvants for the treatment of cancer and infectious diseases and are widely used in the pharmaceutical industry [1,2,3,4,5,6,7,8]. Our group has shown that ECF contained a higher amount of fucose, galactose and sulfate ester group than Macrocystis pyrifera fucodian, Undaria pinnatifida fucoidan and Fucus vesiculosus fucoidan [18] and it promotes the strongest effect of immune cell activation compared to those fucoidans in human peripheral blood mononuclear cells [20]. The mucosal adjuvant effect of ECF, especially activation of respiratory track immunity, has not been investigated

Methods

Results

Conclusion