Luo Min, Shao Bin, Nie Wen, Wei Xia-Wei, Li Yu-Li, Wang Bi-Lan, He Zhi-Yao, Liang Xiao, Ye Ting-Hong, Wei Yu-Quan
State Key Laboratory of Biotherapy and Laboratory for Aging Research, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, PR China.
Department of medical oncology, Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, PR China.
Sci Rep. 2015 Jun 22;5:11062. doi: 10.1038/srep11062.
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.
λ-角叉菜胶是一种海藻多糖,在基础研究中通常用作促炎剂,然而,λ-角叉菜胶的免疫调节活性如何影响肿瘤微环境仍不清楚。在本研究中,我们发现瘤内注射λ-角叉菜胶可抑制B16-F10和4T1荷瘤小鼠的肿瘤生长,并通过增加肿瘤浸润M1巨噬细胞、树突状细胞(DCs)的数量以及脾脏中更多活化的CD4(+)CD8(+) T淋巴细胞来增强肿瘤免疫反应。此外,λ-角叉菜胶可增强脾脏中IL17A的分泌,并显著提高肿瘤中TNF-α的水平,其中大部分由浸润的巨噬细胞分泌。此外,λ-角叉菜胶在基于OVA的癌症预防和治疗疫苗中表现出有效的佐剂作用,可显著增强抗OVA抗体的产生。毒性分析表明,λ-角叉菜胶具有良好的安全性。因此,λ-角叉菜胶可能既用作有效的抗肿瘤剂,又用作癌症免疫治疗中的有效佐剂。