The purpose of this blog post is to present the findings from the study titled “Immunopotentiation Activity of Fucoidans and Relevance to Cancer Immunotherapy” conducted by Yani Li et al. The study sheds light on the current advancements and knowledge regarding the immune-boosting effects of different Fucoidans, while also exploring the potential benefits of combining Fucoidans with immunotherapy.

With advancements in research, our comprehension of the immunomodulatory effects of fucoidan has greatly advanced. Its capability to stimulate CTL-mediated cytotoxicity against cancer cells, along with its potent antitumor properties and excellent safety record, positions it as a highly desirable option for successful cancer immunotherapy.

In the early 1980s, the potential of fucoidan to bolster immune responses was first recognized. Subsequently, researchers have made remarkable progress over the past two decades, substantially expanding our knowledge about the immunomodulatory abilities of fucoidan.

Scientific evidence has established that Fucoidan enhances both the adaptive and innate immune responses. (See Figure 1). Through its interactions with DCs, macrophages, NK cells, T cells, and B cells, fucoidan demonstrates a wide range of immunomodulatory and immunoenhancing effects. It can effectively inhibit the secretion of TNF-α, IFN-γ, and interleukin-6 (IL-6). Fucoidan activates macrophages and NK cells as a mechanism to induce antitumor immunity depending on dose and molecular weight. However, the influence of these substances on CAR-T cells and other modified immune cells is not well understood.

There is growing evidence that suggests the advantages of combining fucoidan with immunotherapeutic agents like ICIs and CAR-T cells for cancer treatment. The use of immunotherapy, such as immune checkpoint inhibitors and CAR-T cell therapy, has revolutionized the treatment of related cancers, producing remarkable clinical outcomes. Fucoidan, a naturally occurring polysaccharide, has been found to have low toxicity and possesses antitumor properties as well as immune-enhancing effects in both animal models and humans. This polysaccharide is a potent agonist of TLR4 that induces human DC activation. Thus, fucoidan could be a promising option for effective cancer immunotherapy.

The study involved examining the immune response to fucoidan by co-culturing CD8+ T cells with human breast cancer cells (MCF-7), and it was discovered that both the number of CD8+ T cells and interferon-γ (IFN-γ) doubled in the body.

Additionally, if fucoidan boosts IL-12 production in the presence of Th1 and Tc1 cells, it could potentially enhance Th1 and Tc1 immune responses, as these responses rely on IL-12 production. This study also demonstrated that fucoidan can be used as an adjuvant to enhance T cell responses by upregulating the production of IFN-γ and increasing the proliferation of CD44+ CD4 cells and memory T cells. These findings suggest that fucoidan directly induces immune responses in CD4 and CD8 T cells and acts as an adjuvant to enhance T-cell immune responses.

In their study, Yang et al. found that fucoidan derived from Ascophyllum nodosum and Fucus vesiculosus directly stimulated the proliferation and activation of CD8+ T cells by upregulating the secretion of IFN-γ and TNF-α. In addition, gene set enrichment analysis (GSEA) revealed that fucoidan promotes CD8+ T cell activation through the JAK/STAT pathway. It was revealed that the fucoidan treatment group improved proliferation and some representative genes within the JAK/STAT pathway were increased in the fucoidan treatment group. The T-cell receptor (TCR) complex has a significant impact on the activation and growth of CD8+ T cells. It also interacts with the TCR/CD3 complex to enhance the activation and proliferation of CD8+ T cells.

In another research study, it was found that the administration of intranasal fucoidan (from Ecklonia cava) resulted in elevated levels of IFN-γ and TNF-α in CD8 and CD4 T cells in the mesenteric lymph nodes of both C57BL/6 and BALB/c mice. This study explored a new administration route of fucoidan in mice and also showed that fucoidan can activate T cells and promote T cell proliferation by increasing the production levels of IFN-γ and TNF-α. Furthermore, according to Lee et al., a study demonstrated that a fucoidan-enriched extract from wakame seaweed effectively countered the effects of cyclophosphamide (CP) by increasing the levels of cytokines (IFN-γ, TNF-α) and plasma antibodies (IgM, total IgG). It showed a significant increase in the proliferation of CD4+ and CD8+ T cells in immunosuppressed mice. These results suggest that IFN-γ and TNF-α are two important effectors involved in fucoidan-induced immunological effects on CD4+ and CD8+ T cells, especially T cell activation and proliferation.

Fucoidan activates DC maturation via Toll-like receptors. When Toll-like receptors (TLRs) are activated, they can change how dendritic cells (DCs) communicate with T cells by modifying three types of signals that DCs send to promote the proliferation and differentiation of T cells into effector cells. can. LMWF from wakame stimulates DC maturation by activating Toll-like receptor 4 (TLR4) and its downstream MAPK and NF-κB signaling pathways and upregulates CD40, CD86, MHC I, and MHC II.

Fucoidan has the potential to play a significant role in the future of cancer immunotherapy due to its ability to enhance the immune system, reduce inflammation, and exhibit anti-tumor properties. However, it is clear that further clinical investigations are warranted to explore the therapeutic properties of fucoidan. In addition, fucoidan holds immense promise as a potential candidate for nanoparticle development and as a part of novel cancer treatment strategies in combination with other immunotherapeutic agents. The extraction method used for fucoidan must be carefully considered as it greatly affects its structural composition and bioactive properties. The hope is that with time, these problems will be gradually overcome.

Source: Mar Drugs. 2023 Feb; 21(2): 128. doi: 10.3390/md21020128