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

• Published in: Cellular immunology 2012-03, Vol.276 (1-2), p.153-161
• Main Authors: Koizumi, Shin-ichi, Masuko, Kazutaka, Wakita, Daiko, Tanaka, Sachi, Mitamura, Rieko, Kato, Yoshihiro, Tabata, Homare, Nakahara, Masahiro, Kitamura, Hidemitsu, Nishimura, Takashi
• Format: Article
• Language: English
• Subjects: Adjuvant; Animals; Antigens, Neoplasm - immunology; Cancer immunotherapy; Cancer Vaccines - immunology; Cell Differentiation - drug effects; Cells, Cultured; Cytokines - biosynthesis; Cytokines - immunology; Cytotoxic T lymphocytes; Dendritic cells; Dendritic Cells - cytology; Dendritic Cells - drug effects; Dendritic Cells - immunology; Larix - chemistry; Mice; Mice, Inbred C57BL; Mice, Knockout; Neoplasms - immunology; Neoplasms - therapy; Phytotherapy; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; T-Lymphocytes, Cytotoxic - drug effects; T-Lymphocytes, Cytotoxic - immunology; Toll-like receptor; Toll-Like Receptor 2 - deficiency; Toll-Like Receptor 2 - immunology; Toll-Like Receptor 4 - deficiency; Toll-Like Receptor 4 - immunology; Type-1 immunity
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1016/j.cellimm.2012.05.002

► Extract of Larix Leptolepis (ELL) activates bone marrow-derived dendritic cells. ► The effect of ELL is dependent on Toll-like receptor (TLR) 2- and TLR4. ► ELL enhances induction of antigen-specific cytotoxic T lymphocytes in vivo. ► ELL is a promising adjuvant for cancer immunotherapy. 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.