ArticleInternational journal of molecular sciences2021
Mechanistic Insights of Anti-Immune Evasion by Nobiletin through Regulating miR-197/STAT3/PD-L1 Signaling in Non-Small Cell Lung Cancer (NSCLC) Cells.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 37 citations in OpenAlex.
- Nobiletin in the modified Yiqi Jianpi Decoction enhances the antitumor activity of CD8The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2026Article
- Solasonine suppresses non-small cell lung cancer progression by inhibiting the STAT3/PD-L1 axis.Scientific reports · 2026Article
- Anti-angiogenesis effect of Baiying Juhua Decoction on the non-small cell lung cancer: integrating pharmacology, multi-machine learning and experimental investigation.Bioresources and bioprocessing · 2026Article
- STAT3 at the tumor-immune interface: mechanisms of immune escape and therapeutic opportunities.Frontiers in immunology · 2026Review
- Exploring the Therapeutic Potential of Nobiletin in Nonsmall Cell Lung Cancer.BioMed research international · 2026Review
- Nobiletin Attenuates Adipogenesis and Promotes Browning in 3T3-L1 Adipocytes Through Exosomal miRNA-Mediated AMPK Activation.Current issues in molecular biology · 2025Article
- Nobiletin suppresses nasopharyngeal carcinoma by regulating the KEAP1/NRF2/ARE pathway.Acta biochimica et biophysica Sinica · 2025Article
- Advances in research on flavonoids in tumor immunotherapy (Review).Molecular medicine reports · 2025Review
- Flavonoids in the Treatment of Non-small Cell Lung Cancer via Immunomodulation: Progress to Date.Molecular diagnosis & therapy · 2025Review
- Unveiling the nexus of p53 and PD-L1: insights into immunotherapy resistance mechanisms in hepatocellular carcinoma.American journal of cancer research · 2025Review
- Lipid-Based Nanocarriers for Targeted Gene Delivery in Lung Cancer Therapy: Exploring a Novel Therapeutic Paradigm.Current gene therapy · 2025Review
- The regulatory role of immune microenvironment-related cells and pathways in the pathogenesis of keloids.Frontiers in immunology · 2025Review
- Non-coding RNAs as potential mediators of resistance to lung cancer immunotherapy and chemotherapy.Oncology research · 2025Review
- The Circadian Clock Component RORA Increases Immunosurveillance in Melanoma by Inhibiting PD-L1 Expression.Cancer research · 2024Article
- MicroRNAs as regulators of immune checkpoints in cancer immunotherapy: targeting PD-1/PD-L1 and CTLA-4 pathways.Cancer cell international · 2024Review
- A review of natural products targeting tumor immune microenvironments for the treatment of lung cancer.Frontiers in immunology · 2024Review
- From immune checkpoints to therapies: understanding immune checkpoint regulation and the influence of natural products and traditional medicine on immune checkpoint and immunotherapy in lung cancer.Frontiers in immunology · 2024Review
- Recent advances on high-efficiency of microRNAs in different types of lung cancer: a comprehensive review.Cancer cell international · 2023Review
- Article
- MiRNA-Based Therapies for Lung Cancer: Opportunities and Challenges?Biomolecules · 2023Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Tumor immune escape is a common process in the tumorigenesis of non-small cell lung cancer (NSCLC) cells where programmed death ligand-1 (PD-L1) expression, playing a vital role in immunosuppression activity. Additionally, epidermal growth factor receptor (EGFR) phosphorylation activates Janus kinase-2 (JAK2) and signal transduction, thus activating transcription 3 (STAT3) to results in the regulation of PD-L1 expression. Chemotherapy with commercially available drugs against NSCLC has struggled in the prospect of adverse effects. Nobiletin is a natural flavonoid isolated from the citrus peel that exhibits anti-cancer activity. Here, we demonstrated the role of nobiletin in evasion of immunosuppression in NSCLC cells by Western blotting and real-time polymerase chain reaction methods for molecular signaling analysis supported by gene silencing and specific inhibitors. From the results, we found that nobiletin inhibited PD-L1 expression through EGFR/JAK2/STAT3 signaling. We also demonstrated that nobiletin exhibited p53-independent PD-L1 suppression, and that miR-197 regulates the expression of STAT3 and PD-L1, thereby enhancing anti-tumor immunity. Further, we evaluated the combination ability of nobiletin with an anti-PD-1 monoclonal antibody in NSCLC co-culture with peripheral blood mononuclear cells. Similarly, we found that nobiletin assisted the induction of PD-1/PD-L1 blockade, which is a key factor for the immune escape mechanism. Altogether, we propose nobiletin as a modulator of tumor microenvironment for cancer immunotherapy.
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