Extracts of Larix Leptolepis effectively augments the generation of tumor antigen-specific cytotoxic T lymphocytes via activation of dendritic cells in TLR-2 and TLR-4-dependent manner.
Type-1 immunity plays a crucial role in host defense against various tumors and infectious diseases. Here, we first demonstrated that extract of Larix Leptolepis (ELL), one of the most popular timbers at Hokkaido area in Japan, strongly activated Type-1 immunity. ELL induced production of Type-1 cytokines such as IL-12 and TNF-α from bone marrow-derived dendritic cells (BMDCs) in TLR2- and TLR4-dependent manner and remarkably up-regulated the expression of MHC and co-stimulatory molecules. In addition, antigen-specific CTLs were significantly augmented by the combined administration of ELL, antigen and BMDCs. Finally, we revealed that combination therapy using ELL, antigen and BMDCs significantly inhibited the growth of established tumor in mouse model. Thus, these findings suggested that ELL would be a novel adjuvant for inducing an activation of Type-1-dependent immunity including activation of BMDCs and induction of tumor-specific CTLs, which is applicable to the therapy of cancer and infectious diseases.
Division of Immunoregulation, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan.
Shin-ichi
S
Koizumi
Kazutaka
K
Masuko
Daiko
D
Wakita
Sachi
S
Tanaka
Rieko
R
Mitamura
Yoshihiro
Y
Kato
Homare
H
Tabata
Masahiro
M
Nakahara
Hidemitsu
H
Kitamura
Takashi
T
Nishimura
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D028221:Larix / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000172:deficiency / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000276:immunology*
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D016207:Cytokines; D010936:Plant Extracts; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4