Polysaccharides from Astragalus membranaceus elicit T cell immunity by activation of human peripheral blood dendritic cells.

Astragalus membranaceus is a widely used herbal medicine in Asia. It has been recognized as possessing various biological properties, however, studies on the activity of the A. membranaceus polysaccharide (AMP), a major component of A. membranaceus, on human peripheral blood dendritic cells (PBDCs) have not been thoroughly investigated. In this study, we found that AMP induced changes in dendritic morphology and the upregulation of activation marker expression and inflammatory cytokine production in human blood monocyte-derived dendritic cells (MDDCs). The AMP promoted the activation of both blood dendritic cell antigen 1+ (BDCA1+) and BDCA3+ PBDCs. AMP-induced secretion of cytokines in the peripheral blood mononuclear cells (PBMCs) was mainly due to PBDCs. Finally, activated BDCA1+ and BDCA3+ PBDCs by AMP elicited proliferation and activation of autologous T cells, respectively. Hence, these data demonstrated that AMPs could activate dendritic and T cells in human blood, and may provide a new direction for the application of AMPs in the regulation of human immunity.

Escherichia coli Mimetic Gold Nanorod-Mediated Photo- and Immunotherapy for Treating Cancer and Its Metastasis.

Most cancer-related deaths are due to metastasis or recurrence. Therefore, the ultimate goal of cancer therapy will be to treat metastatic and recurrent cancers. Combination therapy for cancer will be one of trial for effective treating metastasis and recurrence. In this study, Escherichia coli-mimetic nanomaterials are synthesized using Escherichia coli membrane proteins, adhesion proteins, and gold nanorods, which are named E. coli mimetic AuNRs (ECA), for combination therapy against cancer and its recurrence. ECA treatment with 808 nm laser irradiation eliminates CT-26 or 4T1 tumors via a photothermal effect. ECA with laser irradiation induces activation of immune cells in the tumor-draining lymph nodes. The mice cured from CT-26 or 4T1 tumor by ECA are rechallenged with those cancer in the lung metastatic form, and the results showed that ECA treatment for the first CT-26 or 4T1 tumor challenge prevents cancer infiltration to the lung in the second challenge. This preventive effect of ECA against tumor growth in the second challenge is aided by cancer antigen-specific T cell immunity. Overall, these findings show that ECA is a nanomaterial with dual functions as a photothermal therapy for treating primary cancers and as immunotherapy for preventing recurrence and metastasis.

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

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.

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

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.