Prostate cancer is the most common malignant tumor in men, and accounts for 7.1 % of all cancers [1]. It can spread from the prostate to other parts of the body, especially bones and lymph nodes [2]. For a long time, the occurrence and development of cancer have been attributed to malignant cells with the ability of proliferation, invasion, and metastasis. However, tumor growth is not entirely caused by the accumulation of cancer cells; the tumor microenvironment also plays an important role [3]. As a predominant stromal cell type in the tumor microenvironment, cancer-associated fibroblasts (CAFs) can promote tumor growth and induce normal fibroblasts to transition into CAF phenotype and express specific proteins through transforming growth factor [4]. CAFs interact with tumor cells, endothelial cells, and immune cells in anoxic environment and affect tumor immune response by secreting cytokines, chemokines, and angiogenic factors. They can be used as an immunosuppressive factor and regulator of T lymphocytes in the tumor microenvironment and create an immunosuppressive microenvironment [5,6]. Thus, inhibiting and/or reversing the immunosuppressive function induced by CAFs might be an effective method for the treatment of tumors.

Sargassum fusiforme (S. fusiforme) belongs to the genus Sargassum of the Sargassaceae family and mainly grows in coastal areas of China, Japan, South Korea, and North Korea [7]. It is used as a traditional Chinese medicine to treat tumors, scrofula, edema, beriberi, and chronic bronchitis. The water-soluble polysaccharides of S. fusiforme (Harv.) have been reported to increase the proliferation of spleen cells, the levels of cytokines (IL-2, IL-6, IF-γ, TNF-α), and the phagocytic function of peritoneal macrophages in an immunosuppressed mouse model treated with cyclophosphamide [8,9], suggesting that S. fusiforme polysaccharides may have anti-cancer effects by exerting anti-tumor immune response. As suggested, the fucoidans isolated from S. fusiforme exhibit antitumor efficacy on cancer models, with a fucoidan significantly reducing inflammation-associated colorectal tumorigenesis in mice [10], while its fucose-rich polysaccharide SFPS demonstrates potent growth inhibition of HepG2 xenografts in nude mice accompanied by enhanced systemic immunity (elevated TNF-α, IL-1, NO, and IgM) [11]. In addition, a sulfated galactofucooligomers named HFSGF was found to have antitumor activity against human lung cancer A549 cells in vitro and A549 xenograft tumor growth in vivo [12]. These results suggest that fucoidans from S. fusiforme might be potential polysaccharides with antitumor effect. In the Chinese Pharmacopoeia, fucose (Fuc) is selected as the standard to control the quality of S. fusiforme, indicating that fucoidan, a complex sulfated fucan, might be the major bioactive component. Based on the traditional use and modern research of S. fusiforme, we speculate that fucoidans contained in the brown algae may reverse the T cell proliferation-inhibition through the immunosuppression induced by CAFs in the tumor microenvironment of prostate cancer. To verify this hypothesis, the fucoidans from S. fusiforme were prepared and characterized, followed by the evaluation of their potential capacity to antagonize or reverse the CAFs-mediated suppression of T-cell proliferation. As a result, we report the structure of a fucoidan (SFAP-4) with a large molecular weight and its potential antagonism against T cell proliferation-inhibition through the immunosuppression induced by CAFs.