Dendritic cells might be one of key factors for eliciting antitumor effect by chemoimmunotherapy in vivo |
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Authors: | Hiroyuki Mushiake Takuya Tsunoda Mamoru Nukatsuka Kazuya Shimao Masakazu Fukushima Hideaki Tahara |
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Institution: | (1) Department of Surgery and Bioengineering, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokane-dai, Minato-ku, Tokyo, 108-8639, Japan;(2) Cancer Research Laboratory, Hanno Research Center, Taiho Pharmaceutical Co. Ltd., Hanno, Japan |
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Abstract: | In this study, we demonstrated that chemoimmunotherapy using S-1, a novel oral fluoropyrimidine anticancer drug, combined with lentinan (LNT), a (13) glucan, was effective in vivo, and we clarified the augmentation of the function of dendritic cells (DCs) in vivo and in vitro. The survival period of Colon-26–bearing mice treated with S-1+LNT was significantly more prolonged than that of mice treated with S-1 alone (P<0.05). On the other hand, LNT did not prolong the survival period when combined with S-1 in Colon-26–bearing athymic mice. The frequency of CD86+ DCs infiltrated into Colon-26 was increased in mice treated with S-1+LNT, and splenic DCs harvested from mice treated with S-1+LNT showed more potent T-cell proliferation activity than that of DCs from mice treated with S-1 alone (P<0.05). Furthermore, the activity of cytotoxic T lymphocytes (CTLs) in splenocytes of S-1+LNT–treated mice was specific and more potent than that of CTLs from mice treated with S-1 alone (P<0.05). These results suggest that modulation of specific immunity with LNT has a significant role in enhanced antitumor effects through the modification of DC function. We demonstrated that DCs might play an important role in chemotherapy, and the combination therapy of S-1 and LNT presents a promising chemoimmunotherapy, which might lead to better survival for cancer patients. |
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Keywords: | Chemoimmunotherapy Colon-26 CTL DCs Lentinan S-1 Specific immunity |
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