TY - JOUR
T1 - 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
AU - Koizumi, Shin ichi
AU - Masuko, Kazutaka
AU - Wakita, Daiko
AU - Tanaka, Sachi
AU - Mitamura, Rieko
AU - Kato, Yoshihiro
AU - Tabata, Homare
AU - Nakahara, Masahiro
AU - Kitamura, Hidemitsu
AU - Nishimura, Takashi
N1 - Funding Information:
We thank Dr. Shizuo Akira (Osaka University) and for kind donation of TLR2 -/- , TLR4 -/- , and TLR9 -/- mice and Takuko Sawada (Shionogi Pharmaceutical Institute Co. Ltd., Osaka, Japan) for kind donations of IL-2. This work was partially supported by a Grant-in-Aid and a National Project “Knowledge Cluster Initiative” (2nd stage, “Sapporo Biocluster Bio-S”), a Grant-in Aid for Scientific Research (B) (22300331 to T.N.), a Grant-in Aid for Young Scientists (B) (22790370 to H.K. and 22700894 to D.W.) from Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT), and a JSPS Research Fellowship for Young Scientist (22-5171 to SK and 21-2717 to S.T).
PY - 2012/3
Y1 - 2012/3
N2 - 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.
AB - 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.
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U2 - 10.1016/j.cellimm.2012.05.002
DO - 10.1016/j.cellimm.2012.05.002
M3 - Article
C2 - 22677561
AN - SCOPUS:84863862334
VL - 276
SP - 153
EP - 161
JO - Cellular Immunology
JF - Cellular Immunology
SN - 0008-8749
IS - 1-2
ER -
