ArticleJournal for immunotherapy of cancer2024
LKB1 dictates sensitivity to immunotherapy through Skp2-mediated ubiquitination of PD-L1 protein in non-small cell lung cancer.
Article in Journal for immunotherapy of cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Molecular insights and therapeutic implications for the tumor suppressor role of LKB1 in non-small cell lung cancer.Cancer letters · 2026Review
- The role of tumor metabolic reprogramming in acquired anti-PD-1/PD-L1 resistance.Translational lung cancer research · 2026Review
- Post-translational modifications of immune checkpoints: molecular mechanisms, tumor microenvironment remodeling, and therapeutic implications.Journal of biomedical science · 2026Review
- SKP2 in Cancer: From Molecular Regulation to Therapeutic Vulnerabilities and Translational Perspectives.Drug design, development and therapy · 2026Review
- LKB1 dictates sensitivity to immunotherapy through Skp2-mediated ubiquitination of immune checkpoint proteins in HCC with python analysis.Iranian journal of basic medical sciences · 2026Article
- Advanced and underlying therapeutic strategies in transformed small cell lung cancer.Frontiers in medicine · 2026Review
- Molecular mechanisms and potential targeting strategies of ubiquitin‑proteasome system‑mediated PD‑1/PD‑L1 ubiquitination in tumor immune suppression (Review).Oncology reports · 2025Review
- SKP2 at the crossroads of proliferation and immune evasion: a new target in the tumor microenvironment.Precision clinical medicine · 2025Article
- Sinonasal Tract Osteochondromyxoma: Future Directions Beyond Morphologic Description.Head and neck pathology · 2025Article
- Immunohistochemical analysis of p53 and LKB1 as predictive biomarkers of immune checkpoint inhibitor response in non-small cell lung cancer.Translational lung cancer research · 2025Article
- Multifunctional gold nanoparticles: bridging detection, diagnosis, and targeted therapy in cancer.Molecular cancer · 2025Review
- Targeting LKB1/STK11-mutant cancer: distinct metabolism, microenvironment, and therapeutic resistance.Trends in pharmacological sciences · 2025Review
- Article
- Pan-Cancer Computational Analysis of RKIP (International journal of molecular sciences · 2025Article
- Overcoming resistance to immune checkpoint inhibitor in non-small cell lung cancer: the promise of combination therapy.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLoss-of-function mutations of
methodsWe investigated the mutational landscape of
resultsBy using NGS data sets and histological approaches, we demonstrated that LKB1 status was positively associated with PD-L1 protein expression and conferred a T cell-enriched "hot" TME in NSCLC. Patients with good responses to anti-PD-1/PD-L1 immunotherapy possessed a high level of LKB1 and PD-L1. Skp2 emerged as the molecular hub connecting LKB1 and PD-L1, by which Skp2 catalyzed K63-linked polyubiquitination on K136 and K280 residues to stabilize PD-L1 protein. Inhibition of Skp2 expression by short hairpin RNA or its E3 ligase activity by compound #25 abrogated intact expression of PD-L1 in vitro and generated a T cell-excluded "cold" TME in vivo. Thus, the LKB1-Skp2-PD-L1 regulatory loop was crucial for retaining PD-L1 protein expression and manipulation of this pathway would be a feasible approach for TME remodeling.
conclusionLKB1 and Skp2 are required for intact PD-L1 protein expression and TME remodeling in NSCLC. Inhibition of Skp2 resulted in a conversion from "hot" TME to "cold" TME and abrogated therapeutic outcomes of immunotherapy. Screening LKB1 and Skp2 status would be helpful to select recipients who may benefit from anti-PD-1/PD-L1 immunotherapy.
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