ArticleActa pharmaceutica Sinica. B2024
Demethylzeylasteral induces PD-L1 ubiquitin-proteasome degradation and promotes antitumor immunity
Article in Acta pharmaceutica Sinica. B, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Post‑translational modification‑governed immune states in cancer immunity: Biomarker implications for checkpoint competence, tumor visibility and immunotherapy resistance (Review).International journal of oncology · 2026Review
- Mechanistic Links Between Natural Bioactive Molecules and Tumor Immune Microenvironment States in PD-1/PD-L1 Resistance.Biomedicines · 2026Review
- Lactate metabolism and lactylation in female reproductive diseases: From metabolic rewiring to biomarkers and translational therapeutics.Clinical and translational medicine · 2026Review
- Galangin-loaded biomimetic dendritic cells membrane nanovaccine reprograms the ovarian cancer microenvironmentMaterials today. Bio · 2026Article
- Proanthocyanidins enhance antitumor immunity by promoting ubiquitin-proteasomal PD-L1 degradation via stabilization of LKB1 and SYVN1.The Journal of clinical investigation · 2026Article
- Understanding the immunomodulatory mechanisms for natural products that overcome tumor chemoresistance to platinum-based cancer drugs and other treatments.Frontiers in pharmacology · 2026Review
- Stage-Specific Regulation of Ubiquitination Modifications and Prospects for Targeted Therapy in Triple-Negative Breast Cancer.Oncology research · 2026Review
- Regulatory roles of five key USP family deubiquitinases in cancer: from mechanisms to targeted therapy advances.Frontiers in pharmacology · 2026Review
- Multidimensional analysis of deubiquitinating enzymes in colorectal cancer: biological mechanisms and targeted therapeutic strategies.Frontiers in oncology · 2026Review
- Modulation of the tumor microenvironment by the ubiquitin-proteasome system in colorectal cancer.Journal of translational medicine · 2025Review
- Immunoregulatory roles of post-translational modifications in colorectal cancer: mechanisms and therapeutic implications.Cellular and molecular life sciences : CMLS · 2025Review
- Molecular mechanisms and potential targeting strategies of ubiquitin‑proteasome system‑mediated PD‑1/PD‑L1 ubiquitination in tumor immune suppression (Review).Oncology reports · 2025Review
- Uncovering global research frontiers in deubiquitinating enzymes and immunotherapy: A bibliometric study.Human vaccines & immunotherapeutics · 2025Article
- Suppression of tumor growth by GMI, an edible fungal immunomodulatory protein, is associated with targeting GSK3β‑mediated proteasomal degradation of PD‑L1.International journal of molecular medicine · 2025Article
- PD-1/PD-L1 Cancer Immunotherapeutics Reshape Tumor Microenvironment - Clinical Evidence and Molecular Mechanisms for AI-based Precision Medicine.Clinical reviews in allergy & immunology · 2025Review
- Natural vaccine adjuvants from traditional Chinese medicines: Mechanisms to applications.Acta pharmaceutica Sinica. B · 2025Review
- Application of Immune Checkpoint Inhibitors in Cancer.MedComm · 2025Review
- USP5-Mediated PD-L1 deubiquitination regulates immunotherapy efficacy in melanoma.Journal of translational medicine · 2025Article
- Post-translational modifications of cancer immune checkpoints: mechanisms and therapeutic strategies.Molecular cancer · 2025Review
- Bioinformatic analysis of the role of USP22 expression in hepatocellular carcinoma.International journal of clinical and experimental pathology · 2025Article
Corrections and comments
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Authors and funding
18 authors.
Funding
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Abstract
Programmed cell death ligand-1 (PD-L1) is a T cell inhibitory immune checkpoint molecule that interacts with programmed cell death-1 (PD-1) to promote immune escape of tumor cells. Compared with antibody therapies, small molecule drugs show better prospects due to their advantages such as higher bioavailability, better tissue penetration, and reduced risk of immunogenicity. Here, we found that the small molecule demethylzeylasteral (Dem) can significantly downregulate the expression of PD-L1 in colorectal cancer cells and enhance the killing effect of T cells on tumor cells. Mechanistically, Dem binds to the deubiquitinating enzyme USP22 and promotes its degradation, resulting in increased ubiquitination and degradation of PD-L1 through the proteasome pathway. In addition, Dem increased the activity of cytotoxic T cells and reduced the number of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) in tumor-infiltrating lymphocytes (TILs), thereby activating the tumor immune microenvironment and inhibiting the growth of subcutaneous MC38 tumors in C57BL/6 mice. Moreover, we also found that the combination of Dem and CTLA4 antibodies can further improve the efficacy of antitumor therapy. Our study reveals the mechanism by which Dem promotes PD-L1 degradation and suggests that the combination of Dem and CTLA4 antibodies may improve the efficacy of immunotherapy.
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