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.

Highlights

  • Cancer is the main disease that threatens humankind [1]

  • Since Cytotoxic T lymphocytes (CTLs) activation is controlled by cDC1, we examined whether Codium fragile polysaccharides (CFPs) can induce the activation of cDC1 and cDC2

  • Because intranasal administration of CFPs promoted the activation of immune cells in the mediastinal lymph node (mLN), we examined whether CFPs can elicit immunity against Lewis Lung Carcinoma (LLC) in mice

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Summary

Introduction

Cancer is the main disease that threatens humankind [1]. Lung cancer is characterized by a poor prognosis and difficult diagnosis [2,3]. Most patients with lung cancer are diagnosed at an advanced stage of the disease because there are few symptoms [2,3,4]. For late-stage lung cancer, surgery is not effective, and chemotherapy is associated with undesirable side effects [5,6]. Based on the overexpression of oncoproteins in patients, targeted therapy, such as epidermal growth factor or anaplastic lymphoma kinase, is helpful; only a small subgroup of patients are targetable [7]. Various new cancer treatment methods have been developed and applied to lung cancer [7,8,9]

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