Dendritic cells might be one of key factors for eliciting antitumor effect by chemoimmunotherapy in vivo.
In this study, we demonstrated that chemoimmunotherapy using S-1, a novel oral fluoropyrimidine anticancer drug, combined with lentinan (LNT), a beta (1 --> 3) 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.
Mushiake
Hiroyuki
H
Department of Surgery and Bioengineering, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokane-dai, Minato-ku, 108-8639, Tokyo, Japan.
Tsunoda
Takuya
T
Nukatsuka
Mamoru
M
Shimao
Kazuya
K
Fukushima
Masakazu
M
Tahara
Hideaki
H
D000230:Adenocarcinoma / Q000276:immunology / Q000517:prevention & control / Q000628:therapy; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000276:immunology / Q000494:pharmacology*; D015179:Colorectal Neoplasms / Q000276:immunology / Q000517:prevention & control / Q000628:therapy; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D004338:Drug Combinations; D005354:Fibrosarcoma / Q000276:immunology / Q000517:prevention & control / Q000628:therapy; D016219:Immunotherapy, Adoptive; D007912:Lentinan / Q000008:administration & dosage; D008175:Lung Neoplasms / Q000276:immunology / Q000517:prevention & control / Q000628:therapy; D008223:Lymphoma / Q000276:immunology / Q000517:prevention & control / Q000628:therapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy; D010094:Oxonic Acid / Q000008:administration & dosage; D011725:Pyridines / Q000008:administration & dosage; D051381:Rats; D011919:Rats, Inbred Strains; D013154:Spleen / Q000276:immunology; D015996:Survival Rate; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism; D005641:Tegafur / Q000008:administration & dosage
D004338:Drug Combinations; D011725:Pyridines; C079198:S 1 (combination); D005641:Tegafur; D007912:Lentinan; D010094:Oxonic Acid