ArticleMedical sciences (Basel, Switzerland)2021
Programmed Death-Ligand 1 (PD-L1) Expression Is Induced by Insulin in Pancreatic Ductal Adenocarcinoma Cells Pointing to Its Role in Immune Checkpoint Control.
Article in Medical sciences (Basel, Switzerland), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 20 citations in OpenAlex.
- Diabetes Mellitus as an Independent Risk Factor for Unfavorable Prognosis in Patients With Small Cell Lung Cancer.Thoracic cancer · 2026Article
- Synergistic bioinformatics and sophisticated machine learning unveil ferroptosis-driven regulatory pathways and immunotherapy potential in breast carcinoma.Discover oncology · 2025Article
- Worse survival of hepatocellular cancer patients with membranous insulin receptor overexpression.Scientific reports · 2025Article
- Select Endocrine Disorders and Exosomes in Early PDAC Diagnosis.International journal of molecular sciences · 2024Review
- Evaluation of prognostic significance of histopathological characteristics and tumor-infiltrating lymphocytes for pancreatic cancer survival.Scientific reports · 2024Article
- The role of the immunosuppressive PD-1/PD-L1 checkpoint pathway in the aging process and age-related diseases.Journal of molecular medicine (Berlin, Germany) · 2024Review
- Extracellular Interactors of the IGF System: Impact on Cancer Hallmarks and Therapeutic Approaches.International journal of molecular sciences · 2024Review
- In Vitro Simulated Ketogenic Diet Inhibits the Proliferation and Migration of Liver Cancer Cells by Reducing Insulin Production and Down-regulating FOXC2 Expression.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2024Article
- Identification of clinical prognostic factors and analysis of ferroptosis-related gene signatures in the bladder cancer immune microenvironment.BMC urology · 2024Article
- Ferroptosis-related genes prognostic signature for pancreatic cancer and immune infiltration: potential biomarkers for predicting overall survival.Journal of cancer research and clinical oncology · 2023Article
- Effects ofFood and waterborne parasitology · 2023Article
- IGF2: A Role in Metastasis and Tumor Evasion from Immune Surveillance?Biomedicines · 2023Review
- Development and validation of prognostic index based on purine metabolism genes in patients with bladder cancer.Frontiers in medicine · 2023Article
- Glutamine metabolism genes prognostic signature for stomach adenocarcinoma and immune infiltration: potential biomarkers for predicting overall survival.Frontiers in oncology · 2023Article
- Expression and role of the immune checkpoint regulator PD-L1 in the tumor-stroma interplay of pancreatic ductal adenocarcinoma.Frontiers in immunology · 2023Article
- Pyrimidine metabolism regulator-mediated molecular subtypes display tumor microenvironmental hallmarks and assist precision treatment in bladder cancer.Frontiers in oncology · 2023Article
- Review
- Correlation Study on the Expression of INSR, IRS-1, and PD-L1 in Nonsmall Cell Lung Cancer.Journal of oncology · 2022Article
- Insulin-like growth factor-1 signaling in the tumor microenvironment: Carcinogenesis, cancer drug resistance, and therapeutic potential.Frontiers in endocrinology · 2022Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Type-2 diabetes (T2DM) is a risk factor for the development of pancreatic ductal adenocarcinoma (PDAC) and is characterized by insulin resistance and hyperinsulinemia. Besides the well-known growth-promoting activity of insulin or the other members of the Insulin/Insulin-like Growth factor (IGF) axis, we here describe an inducing effect of insulin on PD-L1 expression in PDAC cells. Treatment of the PDAC cell lines BxPc3, A818-6, and T3M4 with insulin increased PD-L1 expression in a time- and dose dependent fashion, as shown by Western blot and qPCR analysis. siRNA mediated knock-down showed that the effects of insulin on PD-L1 depend on the insulin and IGF receptors (InsR and IGFR, respectively). In addition, a crosstalk of insulin-induced ERK activation and Epidermal Growth Factor (EGF) triggered PD-L1 expression. This involves different mechanisms in the three cell lines including upregulation of InsR-A expression in A818-6 and modulation of the adaptor protein Gab1 in BxPc3 cells. As a consequence of the insulin-induced PD-L1 expression, PDAC cells suppress the proliferation of activated human CD8+ T-cells in coculture experiments. The suppression of CD8+ cell proliferation by insulin-pretreated PDAC cells was reversed by PD-1 blockade with Pembrolizumab or by PD-L1 siRNA. Furthermore, the clinical relevance of these observations was supported by detecting a coexpression of cytoplasmic InsR (characteristic for its activation) and PD-L1 in tumor tissues from PDAC patients. Our findings provide a novel insight into the protumorigenic role of insulin in PDAC. Recognizing the impact of insulin on PD-L1 expression as part of the immune privilege, strategies to interfere with this mechanism could pave the way towards a more efficient immunotherapy of PDAC.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.