ArticleCell reports. Medicine2024
Benzosceptrin C induces lysosomal degradation of PD-L1 and promotes antitumor immunity by targeting DHHC3.
Article in Cell reports. Medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- Research trends of protein palmitoylation in cancer from 2004 to 2024: a bibliometric and visualization analysis.Frontiers in oncology · 2025Pooled it
- The role of protein palmitoylation in disease pathogenesis and therapeutic innovation.Annals of medicine · 2026Review
- A 'three-axis synergy' immunotherapeutic strategy for malignant bone tumors based on natural bioactives and bioactive materials.Bioactive materials · 2026Review
- 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
- Multi-Target Antitumor Effects of Natural Products and Approved Drug Repurposing in Non-Small Cell Lung Cancer: Advances in Mechanisms, Combination Regimens, Delivery System Optimization, and Clinical Challenges.International journal of molecular sciences · 2026Review
- Repurposed ethoxzolamide reprograms antitumor immunity through β-TrCP-dependent PD-L1 ubiquitination.Cell reports. Medicine · 2026Article
- Tutorial: strategies for targeting organelles using nanoparticles.Nature protocols · 2026Review
- ADCY7 dictates N-cadherin stability to inhibit HCC metastasis.JHEP reports : innovation in hepatology · 2026Article
- Decoding the crosstalk between ubiquitination and other post-translational modifications in cancer immunity: from mechanisms to clinical prospects.NPJ precision oncology · 2026Review
- TRIM21-mediated degradation of HILPDA overcomes anti-PD-1 immunotherapy resistance in breast cancer by limiting PD-L1 palmitoylation.Oncogene · 2026Article
- Cancer Cell-Intrinsic Cholesterol Induces Lipid-Associated Macrophage Differentiation via SP1 Palmitoylation to Promote Prostate Cancer Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- MS1-96 induces HIP1R-dependent PD-L1 degradation and promotes antitumor immunity in colorectal cancer.Acta pharmacologica Sinica · 2026Article
- Proanthocyanidins enhance antitumor immunity by promoting ubiquitin-proteasomal PD-L1 degradation via stabilization of LKB1 and SYVN1.The Journal of clinical investigation · 2026Article
- Paroxetine repurposing enhances antitumor immunity via SPOP-mediated PD-L1 ubiquitination and proteasomal degradation.Journal of experimental & clinical cancer research : CR · 2026Article
- Post-translational modifications at the crossroads of cancer metabolism and immune regulation: therapeutic opportunities and challenges.International journal of surgery (London, England) · 2026Review
- ZDHHC-Mediated Protein S-Palmitoylation in Cancer: Epigenetic Interfaces, Structural Logic and Therapeutic Targeting.International journal of medical sciences · 2026Review
- The Roles of ProteinCancer communications (London, England) · 2026Review
- Bridging metabolic reprogramming and targeted therapy: the critical role of S-palmitoylation in cancer.Frontiers in cell and developmental biology · 2026Review
- PTPN22 Dephosphorylates CBL to Inhibit PD-L1 Ubiquitination and Drive Immunosuppression in Renal Cell Carcinoma.International journal of biological sciences · 2026Article
- Protein S-acylation: Pathological mechanisms and novel therapeutic targets for diabetic complications.Chinese herbal medicines · 2026Review
Corrections and comments
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Authors and funding
20 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) blockade has become a mainstay of cancer immunotherapy. Targeting the PD-1/PD-L1 axis with small molecules is an attractive approach to enhance antitumor immunity. Here, we identified a natural marine product, benzosceptrin C (BC), that enhances the cytotoxicity of T cells to cancer cells by reducing the abundance of PD-L1. Furthermore, BC exerts its antitumor effect in mice bearing MC38 tumors by activating tumor-infiltrating T cell immunity. Mechanistic studies suggest that BC can prevent palmitoylation of PD-L1 by inhibiting DHHC3 enzymatic activity. Subsequently, PD-L1 is transferred from the membrane to the cytoplasm and cannot return to the membrane via recycling endosomes, triggering lysosome-mediated degradation of PD-L1. Moreover, the combination of BC and anti-CTLA4 effectively enhances antitumor T cell immunity. Our findings reveal a previously unrecognized antitumor mechanism of BC and represent an alternative immune checkpoint blockade (ICB) therapeutic strategy to enhance the efficacy of cancer immunotherapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.