icariside-i has been researched along with Neoplasms* in 1 studies
1 other study(ies) available for icariside-i and Neoplasms
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Icariside I - A novel inhibitor of the kynurenine-AhR pathway with potential for cancer therapy by blocking tumor immune escape.
Although therapeutic antibodies against immune checkpoints such as PD-1/PD-L1 have achieved unprecedented success in clinical tumor patients, there are still many patients who are ineffective or have limited responses to immune checkpoint blockade (ICB). Discovery of novel strategies for cancer immunotherapy including natural small molecules is needed.. Owing to its extremely low content in Epimedium genus, we firstly constructed a microbial cell factory to enzymatically biosynthesize icariside I, a natural flavonoid monosaccharide from Herbal Epimedium. Using a combination of targeted MS-based metabolomics, flow cytometric analysis, and biological assays, the therapeutic potentials of icariside I were subsequently investigated in vivo and in vitro.. We find that icariside I markedly downregulates a series of intermediate metabolites such as kynurenine, kynurenic acid and xanthurenic acid and corresponding key enzymes involved in kynurenine-AhR pathway in both tumor cells and tumor-bearing mice. In vivo, oral administration of icariside I downregulates SLC7A8 and PAT4 transporters and AhR, thus inhibiting nuclear PD-1 in CTLs. Moreover, icariside I significantly upregulates CD8 + T cells in both peripheral blood and tumor tissues of tumor-bearing mice. Consequently, interferon-γ (IFN-γ) secreted by CD8 + T cells suppresses tumor growth through activation of JAK1-STAT1 signaling, thus inducing tumor cell apoptosis.. These results suggest that icariside I could be an effective small molecule drug for tumor immunotherapy by blocking kynurenine-AhR pathway and tumor immune escape. Topics: Animals; Cell Line, Tumor; Flavones; Immunotherapy; Kynurenine; Mice; Neoplasms; Programmed Cell Death 1 Receptor; Tumor Escape; Tumor Microenvironment; Umbelliferones | 2022 |