ArticleCell death & disease2024
Treating ICB-resistant cancer by inhibiting PD-L1 via DHHC3 degradation induced by cell penetrating peptide-induced chimera conjugates.
Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers.
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Who cites it
18 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
- Discovery of Cyclic Peptides Targeting the BRAF Dimer Interface as Dual Inhibitors.ACS pharmacology & translational science · 2026Article
- Decoding the crosstalk between ubiquitination and other post-translational modifications in cancer immunity: from mechanisms to clinical prospects.NPJ precision oncology · 2026Review
- Peptide-Based PROTACs: Transitioning from Static Paradigm to a Dynamic Landscape within Targeted Protein Degradation.Bioconjugate chemistry · 2026Review
- Crosstalk between protein lipidation and ubiquitination in tumor biology.Apoptosis : an international journal on programmed cell death · 2026Review
- Metformin glycyrrhetinic acid binary injectable hydrogel for synergistic tumor immunotherapy via spatiotemporal microenvironment remodeling.Materials today. Bio · 2026Article
- Overcoming tumor microenvironment barriers: transformable and bioinspired nanomedicine strategies for deep tumor penetration.Journal of nanobiotechnology · 2026Review
- MXRA8, a key palmitoylation-related gene, promotes bladder cancer progression via remodeling tumor microenvironment and predicts poor prognosis.BMC urology · 2026Article
- ZDHHC-Mediated Protein S-Palmitoylation in Cancer: Epigenetic Interfaces, Structural Logic and Therapeutic Targeting.International journal of medical sciences · 2026Review
- Uncovering cellular perturbations and key mediator communications in liver cancer using single-cell RNA sequencing.Frontiers in immunology · 2026Article
- Beyond Structure: The Dynamic Role of the Extracellular Matrix Components in Immune Evasion.Cancer 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
- Review
- Post-translational modifications of cancer immune checkpoints: mechanisms and therapeutic strategies.Molecular cancer · 2025Review
- Review
- Applications of cell penetrating peptide-based drug delivery system in immunotherapy.Frontiers in immunology · 2025Review
- S-palmitoylation: a novel insight in the development and immunotherapy of oral squamous cell carcinoma.Journal of Cancer · 2025Review
- Precision-engineered PROTACs minimize off-tissue effects in cancer therapy.Frontiers in molecular biosciences · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The current selection of ligands for both proteins of interest (POI) and E3 ubiquitin ligase significantly restricts the scope of targeted protein degradation (TPD) technologies. This study introduces cell-penetrating peptide-induced chimera conjugates (cp-PCCs) targeting the DHHC3 enzyme involved in PD-L1 palmitoylation. This approach disrupts PD-L1's immunosuppressive function, enhancing anti-tumor immunity. We developed cp-PCCs to degrade DHHC3, directly linking DHHC3-mediated PD-L1 palmitoylation to PD-L1 stability on tumor cells. Our research utilized both in vitro assays and in vivo experiments in immune checkpoint blockade-resistant mouse models. We focused on a CRBN-based cp-PCC named PCC16, which demonstrated a DC50 of 102 nmol for DHHC3 degradation and significantly reduced PD-L1 levels. In resistant models, PCC16 not only robustly downregulated PD-L1 but also exhibited substantial anti-tumor activity in vivo without significant toxicity. This outperformed traditional inhibitors, showcasing the potential of cp-PCC technology to bypass current PROTAC limitations. Our findings suggest that cp-PCCs offer a promising method for targeting PD-L1 through DHHC3 inhibition and support their continued exploration as a versatile tool in cancer immunotherapy, especially for tumors resistant to standard treatments.
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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.