ArticleBMC cancer2019
Insluin and epithelial growth factor (EGF) promote programmed death ligand 1(PD-L1) production and transport in colon cancer stem cells.
Article in BMC cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 54 citations in OpenAlex.
- Physical Exercise in Immunotherapy.Sports medicine - open · 2026Review
- Tumor microenvironment-driven immune evasion in triple-negative breast cancer: mechanisms, clinical challenges, and therapeutic opportunities.Frontiers in immunology · 2026Review
- Breaking Immunosuppression to Enhance Cancer Stem Cell-Targeted Immunotherapy.International journal of biological sciences · 2025Review
- Integrated omics characterization reveals reduced cancer indicators and elevated inflammatory factors after thermal ablation in non-small cell lung cancer patients.Respiratory research · 2024Article
- Baicalin attenuates PD-1/PD-L1 axis-induced immunosuppression in piglets challenged with Glaesserella parasuis by inhibiting the PI3K/Akt/mTOR and RAS/MEK/ERK signalling pathways.Veterinary research · 2024Article
- [Identification of key genes in Wilms tumor based on high-throughput RNA sequencing and their impacts on prognosis and immune responses].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- Investigation of the potential effects of estrogen receptor modulators on immune checkpoint molecules.Scientific reports · 2024Article
- Crosstalk between colorectal CSCs and immune cells in tumorigenesis, and strategies for targeting colorectal CSCs.Experimental hematology & oncology · 2024Review
- Novel Biomarkers for Inflammatory Bowel Disease and Colorectal Cancer: An Interplay between Metabolic Dysregulation and Excessive Inflammation.International journal of molecular sciences · 2023Article
- ACADL suppresses PD-L1 expression to prevent cancer immune evasion by targeting Hippo/YAP signaling in lung adenocarcinoma.Medical oncology (Northwood, London, England) · 2023Article
- The Role of PRMT5 in Immuno-Oncology.Genes · 2023Review
- Suspension culture strategies to enrich colon cancer stem cells.Oncology letters · 2023Article
- IGF2: A Role in Metastasis and Tumor Evasion from Immune Surveillance?Biomedicines · 2023Review
- Review
- Clinicopathological significance of claspin overexpression and its efficacy as a novel biomarker for the diagnosis of urothelial carcinoma.Virchows Archiv : an international journal of pathology · 2022Article
- Dual-sgRNA CRISPR/Cas9 knockout of PD-L1 in human U87 glioblastoma tumor cells inhibits proliferation, invasion, and tumor-associated macrophage polarization.Scientific reports · 2022Article
- Molecular Docking as a Therapeutic Approach for Targeting Cancer Stem Cell Metabolic Processes.Frontiers in pharmacology · 2022Review
- Immunotherapy against programmed death-1/programmed death ligand 1 in hepatocellular carcinoma: Importance of molecular variations, cellular heterogeneity, and cancer stem cells.World journal of stem cells · 2021Review
- Programmed Death-Ligand 1 (PD-L1) Expression Is Induced by Insulin in Pancreatic Ductal Adenocarcinoma Cells Pointing to Its Role in Immune Checkpoint Control.Medical sciences (Basel, Switzerland) · 2021Article
- Immune evasion by cancer stem cells.Regenerative therapy · 2021Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundProgrammed cell death ligand 1 (PD-L1) is an important immune-inhibitory protein expressed on cancer cells to mediate cancer escape through interaction with PD-1 expressed on activated T lymphocytes (T cells). Previously, we reported that colon and breast cancer stem cells (CSCs) expressed much higher levels of PD-L1 than their parental cells, suggesting they will be more resistant to immune attack.
methodsWe investigated the underlining mechanism of PD-L1 increase in colon CSCs, with a special focus on the effect of insulin and epithelial growth factor (EGF), the two fundamental components to sustain the metabolism and stemness in the culture of CSCs.
resultsWe found that insulin increased the total and surface PD-L1 levels through PI3K/Akt/mTOR pathway as the increase could be inhibited by the dual inhibitor of the pathway, BEZ235. EGF didn't affect the total PD-L1 levels of CSCs but increased the cell surface protein levels by flow cytometry analysis, indicating EGF promotes the transport of PD-L1 to the cell surface. Blocking cell surface PD-L1 with a specific antibody resulted in a significant reduction of tumour sphere formation but didn't interfere with the sphere growth, suggesting that cell surface PD-L1 may act as an adhering molecule for CSCs.
conclusionsApart from the essential roles in metabolism and stemness, insulin and EGF involve in up-regulation of PD-L1 expression in colon CSCs, therefore the inhibition of insulin and EGF/EGFR pathways can be considered for cancer immunotherapy or combined with PD-1/PD-L1 antibody-based cancer immunotherapy to eliminate CSCs.
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