Fucoidan inhibits CCL22 production through NF-κB pathway in M2 macrophages: a potential therapeutic strategy for cancer

Abstract

In tumor microenvironment, macrophages as a polarized M2 population promote tumor progression via releasing multiple cytokines and chemokines. A brown seaweed fucose-rich polysaccharide, fucoidan has antitumor activity and immune modulation through affecting tumor cells and lymphocytes. Here, we focused on the effect of fucoidan on macrophages especially M2 subtype. Our results demonstrated that fucoidan down-regulated partial cytokines and chemokines, especially a M2-type chemokine CCL22. Furthermore, fucoidan inhibited tumor cells migration and CD4+ T lymphocytes, especially Treg cells, recruitment induced by M2 macrophages conditioned medium through suppression of CCL22. Mechanismly, fucoidan inhibited CCL22 via suppressing p65-NF-κB phosphorylation and nuclear translocation. In addition, p38-MAPK and PI3K-AKT also affected the expression of CCL22 through differential modulation of NF-κB transcriptional activity. Taken together, we reveal an interesting result that fucoidan can inhibit tumor cell migration and lymphocytes recruitment by suppressing CCL22 in M2 macrophages via NF-κB-dependent transcription, which may be a novel and promising mechanism for tumor immunotherapy.

Micro RNA Expression after Ingestion of Fucoidan; A Clinical Study

“…This surface-activity of fucoidan is also reflected by the prediction of fucoidan effects on focal adhesion in the present study, which supports previous observations that low molecular weight fucoidan can attenuate aortic aneurism [15]. Additionally, research into fucoidan effects via MAPK cascade includes curative effects on leishmaniosis [18], affecting M2 type macrophages, inhibiting cancer growth by modulating immune responses [19], and reducing cerebral reperfusion injury [20]. Fucoidan interferes with the binding of cancer cells to extracellular matrix [34].…”

Oligo-Fucoidan Prevents M2 Macrophage Differentiation and HCT116 Tumor Progression

“…Fucoidan also regulates immune responses that affect the production of chemokines and proinflammatory cytokines as well as the number and activity of immune cells [46][47][48][49]. For example, the expression of the M2-type chemokine CCL22 through the NF-κB pathway in M2 macrophages is downregulated by Fucoidan [50], which may inhibit tumor cell migration and regulatory T cell recruitment. These suggest that Fucoidan supplementation may alter cancer immunity that helps disease treatment.…”

Dual pH-sensitive nanodrug blocks PD-1 immune checkpoint and uses T cells to deliver NF-κB inhibitor for antitumor immunotherapy

“…These results could be attributed to the TME acidity-increased positive surface charge via partial PDPA protonation to facilitate the cell uptake of nanodrug and the lysosomal acidity-triggered intracellular CUR release, which markedly increased the in vivo performance of CUR to inhibit the NF-B signaling pathway in tumor cells and TAMs. As CCL-22 has proved to modulate the tumor trafficking of T reg cells (8,22), the amounts of T reg cells (CD4 + Foxp3 + ) in tumor tissue of animals receiving different treatments were measured by flow cytometry. The CUR@PPC treatment significantly decreased the percentage of T reg cells in the tumor, as compared to the CUR-S treatment (3.6% versus 8.9%) or the PBS treatment (3.6% versus 16.7%) ( Fig.…”

“…Meanwhile, the CCL-22, a CC-chemokine subfamily member secreted by tumor cells and TAMs, may recruit the T reg cells to the tumor (7), which makes the suppression of CCL-22 secretion a potential means to reduce T reg cells in the tumor. Studies have shown that the expression levels of CCL-22, TGF-, and IL-10 are closely related to the nuclear factor  light-chain enhancer of activated B cells (NF-B) signaling pathway and the suppression of the NF-B pathway in cancer cells and TAMs may substantially inhibit the expressions of all these cytokines (8). Therefore, an NF-B pathway inhibitor is likely to reduce the tumor immune evasion, which can be expected to synergize with an immune checkpoint in-hibitor such as the anti-PD-1 antibody (aPD-1) to improve antitumor immunotherapy.…”