Nasal Administration of Durvillaea antarctica Fucoidan Inhibits Lung Cancer Growth in Mice Through Immune Activation

<b>Background:</b> Various studies have demonstrated fucoidan's immunomodulatory effects. A previous study reported the anticancer effects of <i>Durvillaea antarctica</i> fucoidan (DAF) via immune activation in mice. <b>Methods:</b> In this study, we confirmed the DAF's pulmonary immune activation ability by nasal administration of the dendritic cells (DCs) and T cells. Furthermore, we examined its ability to enhance the efficacy of lung cancer treatment by combining it with anti-PD-L1 antibodies to activate the lung immune response. <b>Results:</b> Nasal DAF administration increased C-C chemokine receptor type 7 expression in DCs and promoted DC migration to the mediastinal lymph nodes (mLN). Specifically, DAF increased conventional DC type 1 (cDC1) and cDC2 numbers in mLN and potently activated cDC1. Furthermore, the nasal administration of DAF increased the production of inflammatory cytokines in the lungs and peripheral blood. Repeated intranasal administration of DAF induced T-cell activation, resulting in the enhanced production of interferon-gamma and tumor necrosis factor-alpha in CD4 T and CD8 T cells. CD8 T cells also showed increased secretion of cytotoxic mediators after DAF treatment, and the proportion of Tregs expressing FoxP3 decreased in the mLN. DAF inhibited lung cancer growth in Lewis lung carcinoma 2 cells, which was enhanced by combining it with an anti-programmed death-ligand 1 antibody. Finally, the anticancer effects of DAF were not observed in mice with depleted CD4-positive and CD8-positive cells. <b>Conclusions:</b> Nasal administration of DAF may inhibit lung cancer growth by inducing lung immune activation and is expected to be helpful as an immune activator for nasal administration.