Antitumor and Adjuvant Activity of λ-carrageenan by Stimulating Immune Response in Cancer Immunotherapy.

Antitumor and Adjuvant Activity of λ-carrageenan by Stimulating Immune Response in Cancer Immunotherapy.
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DOI:
10.1038/srep11062
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发表时间:
2015-06-22
期刊:
影响因子:
4.6
通讯作者:
Wei YQ
Wei YQ
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Luo M;Shao B;Nie W;Wei XW;Li YL;Wang BL;He ZY;Liang X;Ye TH;Wei YQ

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λ-卡拉胶是一种海藻多糖,在基础研究中被广泛用作促炎剂,但λ-卡拉胶的免疫调节活性如何影响肿瘤微环境尚不清楚。本研究发现,瘤内注射λ-卡拉胶可抑制B16-F10和4 T1荷瘤小鼠的肿瘤生长,并通过增加肿瘤浸润的M1巨噬细胞、树突状细胞和脾脏中活化的CD 4 + CD 8 + T淋巴细胞的数量来增强肿瘤免疫应答。此外,λ-卡拉胶还能增强脾脏IL 17 A的分泌,显著提高肿瘤组织TNF-α的水平,其中大部分由浸润的巨噬细胞分泌。此外,λ-卡拉胶在用于癌症治疗的基于OVA的预防性和治疗性疫苗中表现出有效的佐剂作用,这显著增强了抗OVA抗体的产生。毒性分析表明λ-卡拉胶具有良好的安全性。因此,λ-卡拉胶可能既作为一种有效的抗肿瘤剂,又作为一种有效的癌症免疫治疗佐剂。
λ-Carrageenan is a seaweed polysaccharide which has been generally used as proinflammatory agent in the basic research, however, how the immunomodulating activity of λ-carrageenan affects tumor microenvironment remains unknown. In this study, we found that intratumoral injection of λ-carrageenan could inhibit tumor growth in B16-F10 and 4T1 bearing mice and enhance tumor immune response by increasing the number of tumor-infiltrating M1 macrophages, DCs and more activated CD4+CD8+ T lymphocytes in spleen. In addition, λ-carrageenan could enhance the secretion of IL17A in spleen and significantly increase the level of TNF-α in tumor, most of which was secreted by infiltrating macrophages. Moreover, λ-carrageenan exhibited an efficient adjuvant effect in OVA-based preventative and therapeutic vaccine for cancer treatment, which significantly enhanced the production of anti-OVA antibody. The toxicity analysis suggested that λ-carrageenan was with a good safety profile. Thus, λ-carrageenan might be used both as a potent antitumor agent and an efficient adjuvant in cancer immunotherapy.
通过淋巴结消除来清除稳态细胞因子下沉,增强了采用转移的肿瘤特异性CD8+ T细胞的功效。
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