ArticleBritish journal of cancer2024
Epithelial-mesenchymal transition induced by tumor cell-intrinsic PD-L1 signaling predicts a poor response to immune checkpoint inhibitors in PD-L1-high lung cancer.
Article in British journal of cancer, 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 35 papers.
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Who cites it
35 citing papers in PubMed.
- Distinct Molecular Pathways Driving Thymic and Pulmonary Neuroendocrine Neoplasms: Organ of Origin Defines Molecular Identity and Yields CD44 as a Marker of Pulmonary Neuroendocrine Tumors.Endocrine pathology · 2026Article
- Towards liquid biopsy-based analysis of antitumour immunity.Nature reviews. Clinical oncology · 2026Review
- Oncogenic viral infection triggers LAMP2A SUMOylation and chaperone-mediated autophagy to promote tumorigenesis.Nature microbiology · 2026Article
- S100A10 promotes tumorigenesis and metastasis in lung adenocarcinoma by regulating JUND/TNC axis-mediated EMT.Translational oncology · 2026Article
- Overcoming resistance to immune checkpoint inhibitors in cancer: translational mechanisms, dynamic biomarkers, clinically actionable combination strategies, and comparative checkpoint biology.Immunologic research · 2026Review
- Plasticity of Non-Apoptotic Residual Tumor Cells After Neoadjuvant Immunochemotherapy: Epigenetic and Microenvironmental Determinants.Biomolecules · 2026Review
- Multi-omics profiling unveils biological and clinical insights into pulmonary sarcomatoid carcinoma.Cell reports. Medicine · 2026Article
- Targeting Cathepsin C in Cancer Metastasis: Protease Network Activation, Inflammatory Crosstalk, and Therapeutic Opportunities.International journal of molecular sciences · 2026Review
- Epithelial-mesenchymal transition and immunosuppression: Two sides of the same coin.Cellular and molecular life sciences : CMLS · 2026Review
- Clinico-molecular characteristics and enhanced efficacy of immune checkpoint inhibitors in TP53-mutated advanced biliary tract cancer.Journal of gastroenterology · 2026Article
- Glucose metabolic reprogramming as a driver of immunosuppression in the tumour microenvironment.Clinical and translational medicine · 2026Review
- Bidirectional coupling among EMT, AXL-RB1 signaling and lineage switch drives resistance to osimertinib and worse clinical outcomes in NSCLC.bioRxiv : the preprint server for biology · 2026Article
- Kukoamine B Inhibits EMT in Lung Adenocarcinoma Cells by Regulating Intracellular PD-L1-Mediated p65 Nuclear Translocation.Biology · 2026Article
- IGSF9 promotes immunotherapy resistance in colon cancer by orchestrating an immunosuppressive tumor microenvironment and enables combinatorial targeting strategies.Biochemistry and biophysics reports · 2026Article
- Regulatory network and spatial modeling reveal cooperative mechanisms of resistance and immune escape in ER+ breast cancer.BMC cancer · 2026Article
- Reciprocal regulation of hMENA and TGF-β signaling in cancer-associated fibroblasts promotes EMT, immunosuppression, poor prognosis, and ICT resistance in NSCLC.Journal for immunotherapy of cancer · 2026Article
- Interferon-gamma signaling pathway: Modulation of key genes in the progression of glioblastoma.World journal of biological chemistry · 2025Review
- 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
- Treatment of NSCLC after chemoimmunotherapy - are we making headway?Nature reviews. Clinical oncology · 2025Review
- EMT and cancer stem cells: Drivers of therapy resistance and promising therapeutic targets.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2025Review
Corrections and comments
- Erratum issued
Authors and funding
11 authors.
Funding
Abstract
backgroundWe investigated the role of tumor cell-intrinsic PD-L1 signaling in the epithelial-mesenchymal transition (EMT) in non-small-cell lung cancer (NSCLC) and the role of EMT as a predictive biomarker for immune checkpoint inhibitor (ICI) therapy.
methodsPD-L1-overexpressing or PD-L1-knockdown NSCLC cells underwent RNA-seq and EMT phenotype assessment. Mouse lung cancer LLC cells were injected into nude mice. Two cohorts of patients with NSCLC undergoing ICI therapy were analyzed.
resultsRNA-seq showed that EMT pathways were enriched in PD-L1-high NSCLC cells. EMT was enhanced by PD-L1 in NSCLC cells, which was mediated by transforming growth factor-β (TGFβ). PD-L1 promoted the activation of p38-MAPK by binding to and inhibiting the protein phosphatase PPM1B, thereby increasing the TGFβ production. Tumor growth and metastasis increased in nude mice injected with PD-L1-overexpressing LLC cells. In the ICI cohort, EMT signature was higher in patients with progressive disease than in those with responses, and EMT was significantly associated with poor survival in PD-L1-high NSCLC. In PD-L1-high NSCLC, EMT was associated with increased M2-macrophage and regulatory T-cell infiltrations and decreased cytotoxic T-cell infiltration.
conclusionsTumor cell-intrinsic PD-L1 function contributes to NSCLC progression by promoting EMT. EMT may predict an unfavorable outcome after ICI therapy in PD-L1-high NSCLC.
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