ArticleCancer science2019
Hypoxia-inducible factor-1α and nuclear factor-κB play important roles in regulating programmed cell death ligand 1 expression by epidermal growth factor receptor mutants in non-small-cell lung cancer cells.
Article in Cancer science, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 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
40 citing papers in PubMed, 56 citations in OpenAlex.
- The distinct roles of ROS in tumor immunity: from mechanisms to immunotherapeutic applications.Journal of hematology & oncology · 2026Review
- Immune-tumor cell ligand-receptor axes driving metabolic reprogramming and therapeutic resistance in cancer.Frontiers in immunology · 2026Review
- Article
- PD-L1 expression in primary lung tumor as a superior predictive biomarker to metastatic lymph nodes for first-line immunochemotherapy in advanced KRAS-mutant non-small cell lung cancer.Translational lung cancer research · 2025Article
- High-expression of BCL10 inhibits cell-mediated immunity within the tumor immune microenvironment.Frontiers in immunology · 2025Article
- Multiple signaling pathways in the frontiers of lung cancer progression.Frontiers in immunology · 2025Review
- The role of EGFR mutations in sensitivity of PD-1/PD-L1 blockade in non-small cell lung cancer.American journal of cancer research · 2025Review
- The CLCF1-CNTFR axis drives an immunosuppressive tumor microenvironment and blockade enhances the effects of established cancer therapies.Research square · 2024Article
- Targeting the NF-κB pathway as a potential regulator of immune checkpoints in cancer immunotherapy.Cellular and molecular life sciences : CMLS · 2024Review
- From immune checkpoints to therapies: understanding immune checkpoint regulation and the influence of natural products and traditional medicine on immune checkpoint and immunotherapy in lung cancer.Frontiers in immunology · 2024Review
- p66Shc deficiency in CLL cells enhances PD-L1 expression and suppresses immune synapse formation.Frontiers in cell and developmental biology · 2024Article
- Molecular Farming of Pembrolizumab and Nivolumab.International journal of molecular sciences · 2023Review
- PD-L1: expression regulation.Blood science (Baltimore, Md.) · 2023Review
- Targeting immune cell types of tumor microenvironment to overcome resistance to PD-1/PD-L1 blockade in lung cancer.Frontiers in pharmacology · 2023Review
- [Research Progress of Anti-PD-1/PD-L1 Therapy for Non-small Cell Lung Cancer with EGFR Mutation].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2022Article
- TMEM16A as a potential treatment target for head and neck cancer.Journal of experimental & clinical cancer research : CR · 2022Review
- Quantifying the contribution of transcription factor activity, mutations and microRNAs to CD274 expression in cancer patients.Scientific reports · 2022Article
- Demethylase JMJD2D induces PD-L1 expression to promote colorectal cancer immune escape by enhancing IFNGR1-STAT3-IRF1 signaling.Oncogene · 2022Article
- Extracellular vesicle PD-L1 in reshaping tumor immune microenvironment: biological function and potential therapy strategies.Cell communication and signaling : CCS · 2022Review
- Potential Role of CXCL13/CXCR5 Signaling in Immune Checkpoint Inhibitor Treatment in Cancer.Cancers · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Some driver gene mutations, including epidermal growth factor receptor (EGFR), have been reported to be involved in expression regulation of the immunosuppressive checkpoint protein programmed cell death ligand 1 (PD-L1), but the underlying mechanism remains obscure. We investigated the potential role and precise mechanism of EGFR mutants in PD-L1 expression regulation in non-small-cell lung cancer (NSCLC) cells. Examination of pivotal EGFR signaling effectors in 8 NSCLC cell lines indicated apparent associations between PD-L1 overexpression and phosphorylation of AKT and ERK, especially with increased protein levels of phospho-IκBα (p-IκBα) and hypoxia-inducible factor-1α (HIF-1α). Flow cytometry results showed stronger membrane co-expression of EGFR and PD-L1 in NSCLC cells with EGFR mutants compared with cells carrying WT EGFR. Additionally, ectopic expression or depletion of EGFR mutants and treatment with EGFR pathway inhibitors targeting MEK/ERK, PI3K/AKT, mTOR/S6, IκBα, and HIF-1α indicated strong accordance among protein levels of PD-L1, p-IκBα, and HIF-1α in NSCLC cells. Further treatment with pathway inhibitors significantly inhibited xenograft tumor growth and p-IκBα, HIF-1α, and PD-L1 expression of NSCLC cells carrying EGFR mutant in nude mice. Moreover, immunohistochemical analysis revealed obviously increased protein levels of p-IκBα, HIF-1α, and PD-L1 in NSCLC tissues with EGFR mutants compared with tissues carrying WT EGFR. Non-small-cell lung cancer tissues with either p-IκBα or HIF-1α positive staining were more likely to possess elevated PD-L1 expression compared with tissues scored negative for both p-IκBα and HIF-1α. Our findings showed important roles of phosphorylation activation of AKT and ERK and potential interplay and cooperation between NF-κB and HIF-1α in PD-L1 expression regulation by EGFR mutants in NSCLC.
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.