Journal
CARBOHYDRATE POLYMERS
Volume 263, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.carbpol.2021.117967
Keywords
Adjuvant; Sarcandra glabra; Natural polysaccharide; Cancer vaccine; Immune response
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Funding
- National Key Research and Development Program of China [2018YFA0902000]
- National Natural Science Foundation of China [81673589, 81973222, 82073754]
- Natural Science Foundation of Jiangsu Province [BK20191317]
- Double First-Class University Project [CPU 2018GF08]
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The study found that the acidic polysaccharide p-SGP from Sarcandra glabra is an ideal adjuvant for tumor vaccines, enhancing anti-tumor immunity, inhibiting tumor growth and metastasis, promoting dendritic cells maturation and Th1 immune response. p-SGP activates DCs through the TLR4 receptor and up-regulates DLL4 gene in the Th1 and Th2 cell differentiation pathway, suggesting a unique mechanism for enhancing anti-tumor immunity.
Immunological adjuvants are an important part of tumor vaccines and are critical for stimulating anti-tumor immune responses. However, the clinical needs of strong adjuvants have not been met. In this work, we found that the purified acidic polysaccharide from Sarcandra glabra, named p-SGP, is an ideal adjuvant for tumor vaccines. Cancer vaccines could induce stronger humoral and cellular immune responses when they are adjuvanted with p-SGP. Compared with CpG, a well-studied adjuvant, p-SGP significantly augmented the anti-tumor immunity of various cancer vaccines, which is leading to noticeable inhibition of tumor growth and metastasis in tumor-bearing mice. Moreover, p-SGP promoted dendritic cells (DCs) maturation and Th1-polarized immune response. Toll-like receptor 4 (TLR4) inhibitor TAK-242 could significantly inhibit the expression of mature molecules on the surface of DCs stimulated by p-SGP, suggesting that p-SGP could play the role of activating DCs through the TLR4 receptor. Results of RNA-seq showed that the Delta-like ligand 4 (DLL4) gene in the pathway Th1 and Th2 cell differentiation was significantly up-regulated in the DCs treated with p-SGP, suggesting that pSGP has a unique mechanism of enhancing anti-tumor immunity.
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