Abstract
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.
Highlights
Most patients with cancer receive surgery, radiation therapy, chemotherapy or combination of these treatments
The intratumoral injection of λ -carrageenan led to a significant reduction in tumor volumes while compared with normal saline groups in three tumor models (Fig. 1)
We noticed that λ -carrageenan had more potent antitumor effect in B16-F10 tumor model, we chose B16-F10 tumor as the model to further study how λ -carrageenan affected the microenvironment in tumors
Summary
Min Luo1,*, Bin Shao1,*, Wen Nie2,*, Xia-Wei Wei[1], Yu-Li Li1, Bi-Lan Wang[1], Zhi-Yao He1, Xiao Liang[1], Ting-Hong Ye1 & Yu-Quan Wei[1] λ-Carrageenan is a seaweed polysaccharide which has been generally used as proinflammatory agent in the basic research, how the immunomodulating activity of λ-carrageenan affects tumor microenvironment remains unknown. As λ -carrageenan significantly stimulated tumor immune response and increased the influx of F4/80low macrophages and DCs which are very important cells in the antigen presenting process, we hypothesized that the λ -carrageenan might be used as a potential adjuvant in cancer immunotherapy. The H&E staining of vital organs from the λ -carrageenan treated mice showed no abnormalities while compared with controls Based on these results, we draw a conclusion that λ -carrageenan is a potent anti-tumor agent while administered intratumoraly or used as an adjuvant in tumor vaccine, which inhibited tumor growth through stimulating immune response while exhibiting no toxicities to other vital organs. The intratumoral injection of λ -carrageenan significantly induced the infiltration of M1 macrophages (detected as CD11b+F4/80low in flow cytometry) in tumor tissues and increased the production of proinflammatory cytokines which helped to improve the tumor immune response together with the infiltrated DCs and activated lymphocytes. We conclude that λ -carrageenan is a potent antitumor agent and efficient adjuvant which might be further used in cancer treatment to enhance tumor immune response
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