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

Koizumi, Shin; Masuko, Kazutaka; Wakita, Daiko; Tanaka, Sadao; Mitamura, Rieko; Kato, Yoshihiro; Tabata, Homare; Nakahara, Masahiro; Kitamura, Hiroyuki; Nishimura, Takashi

doi:10.1016/j.cellimm.2012.05.002

Cited by 14 publications

(12 citation statements)

References 65 publications

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“…[47] TLR2 and TLR4 agonist, extract of larix leptolepis (ELL), activates bone marrow-derived dendritic cells (BMDCs) to induce the production of cytokines IL-12 and TNF-а, and induces tumor-specific cytotoxic T lymphocytes (CTLs) against cancer. [48] TLR2 ligand HP-NAP ( Helicobacter pylori neutrophil activating protein) is a potential therapeutic agent for nonmuscle invasive bladder cancer. HP-NAP is able to enhance the induction of the T helper 1 (TH1) cell differentiation and reduce vascularization of cancer through induction of IFN-γ.…”

Section: Resultsmentioning

confidence: 99%

Application potential of toll-like receptors in cancer immunotherapy

Shi

Chen

et al. 2016

Medicine

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Toll-like receptors (TLRs), as the most important pattern recognition receptors in innate immunity, play a pivotal role in inducing immune response through recognition of microbial invaders or specific agonists. Recent studies have suggested that TLRs could serve as important regulators in the development of a variety of cancer. However, increasing evidences have shown that TLRs may display quite opposite outcomes in cancer development. Although several potential therapeutic Toll-like receptor ligands have been found, the mechanism and therapy prospect of TLRs in cancer development has to be further elucidated to accelerate the clinical application. By performing a systematic review of the present findings on TLRs in cancer immunology, we attempted to evaluate the therapeutic potential of TLRs in cancer therapy and elucidate the potential mechanism of cancer progress regulated by TLR signaling and the reported targets on TLRs for clinical application. An electronic databases search was conducted in PubMed, Chinese Scientific Journal Database, and Chinese Biomedical Literature Database from their inception to February 1, 2016. The following keywords were used to search the databases: Toll-like receptors, cancer therapy, therapeutic target, innate immunity. Of 244 studies that were identified, 97 nonrelevant studies were excluded. In total, 147 full-text articles were assessed, and from these, 54 were excluded as they did not provide complete key information. Thus, 93 studies were considered eligible and included in the analysis. According to the data from the included trials, 14 TLR ligands (77.8%) from 82 studies have been demonstrated to display antitumor property in various cancers, whereas 4 ligands (22.2%) from 11 studies promote tumors. Among them, only 3 TLR ligands have been approved for cancer therapy, and 9 ligands were in clinical trials. In addition, the potential mechanism of recently reported targets on TLRs for clinical application was also evaluated in this review. We show that targeting TLRs in cancer immunotherapy is a promising strategy for cancer therapy, and the specific TLR ligands, either alone or combination, exhibit antitumor potential.

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Section: Resultsmentioning

confidence: 99%

Application potential of toll-like receptors in cancer immunotherapy

Shi

Chen

et al. 2016

Medicine

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“…Activity of mouse DCs to induce antigen-specific cytotoxic T lymphocytes (CTL) was evaluated in a 51 Cr released assay as described by Koizumi et al [ 17 ]. where 51 Cr–labeled E.G7-OVA or EL4 cells were incubated with cells from the popliteal lymph node of B6 mice after inoculation of the OVA-loaded DCs (2×10 5 ) into the footpad.…”

Section: Methodsmentioning

confidence: 99%

Development of effective tumor immunotherapy using a novel dendritic cell–targeting Toll-like receptor ligand

et al. 2017

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Although dendritic cell (DC)-based immunotherapy shows little toxicity, improvements should be necessary to obtain satisfactory clinical outcome. Using interferon-gamma injection along with DCs, we previously obtained significant clinical responses against small or early stage malignant tumors in dogs. However, improvement was necessary to be effective to largely developed or metastatic tumors. To obtain effective methods applicable to those tumors, we herein used a DC-targeting Toll-like receptor ligand, h11c, and examined the therapeutic effects in murine subcutaneous and visceral tumor models and also in the clinical treatment of canine cancers. In murine experiments, most and significant inhibition of tumor growth and extended survival was observed in the group treated with the combination of h11c-activated DCs in combination with interferon-gamma and a cyclooxygenase2 inhibitor. Both monocytic and granulocytic myeloid-derived suppressor cells were significantly reduced by the combined treatment. Following the successful results in mice, the combined treatment was examined against canine cancers, which spontaneously generated like as those in human. The combined treatment elicited significant clinical responses against a nonepithelial malignant tumor and a malignant fibrous histiocytoma. The treatment was also successful against a bone-metastasis of squamous cell carcinoma. In the successful cases, the marked increase of tumor-responding T cells and decrease of myeloid-derived suppressor cells and regulatory T cells was observed in their peripheral blood. Although the combined treatment permitted the growth of lung cancer of renal carcinoma-metastasis, the marked elevated and long-term maintaining of the tumor-responding T cells was observed in the patient dog. Overall, the combined treatment gave rise to emphatic amelioration in DC-based cancer therapy.

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“…Aqueous extracts of crushed sawdust of Larix Leptolepis (Larix kaempferi), a conifer from subartic regions, were shown to activate type 1 immune responses in mouse bone marrow-derived cells with enhanced induction of cytotoxic T cells (Koizumi et al, 2012). This effect was found to occur through TLR2 and TLR4-dependent pathways but not TLR9.…”

Section: Barkmentioning

confidence: 99%

Plant‐Based Modulation of Toll‐like Receptors: An Emerging Therapeutic Model

Chahal

Sivamani

Isseroff

et al. 2012

Phytotherapy Research

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Plant-based extracts present a large source of natural immune modulators, many of which have been used in traditional medicine for centuries. Recent research efforts have identified plant extracts as potential modulators of Toll-like receptors (TLRs), the first responders in immunological defenses in normal and disease conditions. This review aims to provide a comprehensive discussion of the modulatory effects of plant-based extracts on TLR expression, signaling, and activation. We organized the review by extraction solvent and plant part showing how they impacted the TLRs. The phytochemical components of the extracts discovered to enable these effects are diverse and vary based on the plant part. The role of the extraction solvent and differences between the different phytochemical components, such as phenolics and polysaccharides, are discussed. Plant extracts hold promising treatments for controlling inflammation and, conversely, for stimulating the immune response. Further research is needed to identify bioactive components of the extracts, mechanisms of their action, and in vivo pharmacological effects using appropriate disease models to ultimately adapt the findings for clinical use.

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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

Cited by 14 publications

References 65 publications

Application potential of toll-like receptors in cancer immunotherapy

Application potential of toll-like receptors in cancer immunotherapy

Development of effective tumor immunotherapy using a novel dendritic cell–targeting Toll-like receptor ligand

Plant‐Based Modulation of Toll‐like Receptors: An Emerging Therapeutic Model

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