4.7 Article

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

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出版社

MDPI
DOI: 10.3390/ijms22179125

关键词

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

资金

  1. National Natural Science Foundation of China [81874164]
  2. National Research Foundation of Korea [NRF-2019R1C1C1003334, NRF-2020R1A4A1016029, NRF-2020R1A6A1A03044512]

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Intranasal administration of Ecklonia cava-extracted fucoidan (ECF) was found to induce anti-cancer immunity in the lung by promoting the activation of dendritic cells, natural killer cells, and T cells. Furthermore, ECF enhanced the anti-cancer activities against melanoma and carcinoma tumor growth in the lungs, showing potential as a mucosal adjuvant for enhancing immunotherapeutic effects.
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.

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