ArticleLung cancer (Amsterdam, Netherlands)2023
Chemotherapy-induced PDL-1 expression in cancer-associated fibroblasts promotes chemoresistance in NSCLC.
Article in Lung cancer (Amsterdam, Netherlands), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 13 citations in OpenAlex.
- PD-L1 and PD-L2 regulate in cell-autonomous and N-glycosylation-dependent manners the pro-tumorigenic characteristics and functions of human cancer-associated fibroblasts.Molecular medicine (Cambridge, Mass.) · 2026Article
- Effects of Tumor Microenvironment on Lung Cancer Stem Cells: Bidirectional Regulatory Mechanisms.Cancer medicine · 2026Review
- Insights into the relevance of targeting fibroblasts to control cancer.Cell reports. Medicine · 2025Review
- Hidden forces: the impact of cancer-associated fibroblasts on non-small cell lung cancer development and therapy.Journal of translational medicine · 2025Review
- The Current State of Tumor Microenvironment-Specific Therapies for Non-Small Cell Lung Cancer.Cancers · 2025Review
- CAF-derived exosome-miR-3124-5p promotes malignant biological processes in NSCLC via the TOLLIP/TLR4-MyD88-NF-κB pathway.Oncology research · 2025Article
- Cancer-associated fibroblasts, tumor and radiotherapy: interactions in the tumor micro-environment.Journal of experimental & clinical cancer research : CR · 2024Review
- Exosome crosstalk between cancer stem cells and tumor microenvironment: cancer progression and therapeutic strategies.Stem cell research & therapy · 2024Review
- Statins abrogate gemcitabine-induced PD-L1 expression in pancreatic cancer-associated fibroblasts and cancer cells with improved therapeutic outcome.Cancer immunology, immunotherapy : CII · 2023Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
objectivesA cure for cancer is out of reach for most patients due to chemoresistance. Cancer-associated fibroblasts (CAFs) play a vital role in cancer chemoresistance, but detailed understanding of the process particularly in chemoresistant lung cancer is lacking. In this study, we investigated programmed death-ligand 1 (PDL-1) as a potential biomarker for CAF-induced chemoresistance and evaluated its role and the underlying mechanisms of chemoresistance in non-small cell lung cancer (NSCLC). MATERIALS AND
methodsA systemic search of gene expression profiles of multiple tissues in NSCLC was carried out to determine the expression intensities of traditional fibroblast biomarkers and CAF-secreted protumorigenic cytokines. PDL-1 expression in CAFs was analyzed by ELISA, Western blotting, and flow cytometry. Human cytokine array was used to identify specific cytokines secreted from CAFs. Role of PDL-1 in NSCLC chemoresistance was assessed using CRISPR/Cas9 knockdown and various functional assays including MTT, cell invasion, sphere formation, and cell apoptosis. In vivo experiments were conducted using a co-implantation xenograft mouse model with live cell imaging and immunohistochemistry.
resultsWe demonstrated that chemotherapy-stimulated CAFs promoted tumorigenic and stem cell-like properties of NSCLC cells, which contribute to their chemoresistance. Subsequently, we revealed that PDL-1 expression is upregulated in chemotherapy-treated CAFs and is associated with poor prognosis. Silencing PDL-1 expression suppressed CAFs' ability to promote stem cell-like properties and invasiveness of lung cancer cells, favoring chemoresistance. Mechanistically, an upregulation of PDL-1 in chemotherapy-treated CAFs led to an increase in hepatocyte growth factor (HGF) secretion, which stimulates cancer progression, cell invasion, and stemness of lung cancer cells, while inhibiting apoptosis.
conclusionOur results show that PDL-1-positive CAFs modulate stem cell-like properties of NSCLC cells by secreting elevated HGF, thereby promoting chemoresistance. Our finding supports PDL-1 in CAFs as a chemotherapy response biomarker and as a drug delivery and therapeutic target for chemoresistant NSCLC.
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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 Socratic graph.