ArticleThe Journal of pathology2019
MAPK pathway activity plays a key role in PD-L1 expression of lung adenocarcinoma cells.
Article in The Journal of pathology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
114 citing papers in PubMed, 2 syntheses or guidelines pooled it, 162 citations in OpenAlex.
- Prognostic value of programmed cell death ligand 1 expression in patients with intrahepatic cholangiocarcinoma: a meta-analysis.Frontiers in immunology · 2023Pooled it
- Prognostic role of different PD-L1 expression patterns and tumor-infiltrating lymphocytes in high-grade serous ovarian cancer: a systematic review and meta-analysis.Frontiers in immunology · 2023Pooled it
- Second-line chemoimmunotherapy with nivolumab and paclitaxel in immune-related biomarker-enriched advanced gastric cancer: a multicenter phase Ib/II study.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2024Trial
- A single arm phase Ib/II trial of first-line pembrolizumab, trastuzumab and chemotherapy for advanced HER2-positive gastric cancer.Nature communications · 2022Trial
- RAD001-Adjuvanted Influenza Vaccine Synergizes With Anti-Programmed Cell Death Protein 1 Therapy to Enhance Antitumor Immunity in Programmed Cell Death Ligand 1-Low Murine Lung Cancer.World journal of oncology · 2026Article
- Macrophages as Drivers of Resistance to Dabrafenib Plus Trametinib Therapy in Anaplastic Thyroid Cancer.International journal of molecular sciences · 2026Article
- Article
- Drug-tolerant persisters and immunotherapy persister cells exhibit cross-resistance and share common survival mechanisms.Cell death and differentiation · 2026Article
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- PD-L1 expression scoring using artificial intelligence algorithms in non-small cell lung cancer harbouring ROS1 fusions: potential clinical-biological significance.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- Targeting metabolic-epigenetic-immune axis in cancer: molecular mechanisms and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- Neoadjuvant sintilimab, albumin-bound paclitaxel, and carboplatin for locally advanced, resectable esophageal squamous cell carcinoma: clinical study and mechanistic exploration.NPJ precision oncology · 2026Article
- KRAS mutations as architects of the tumor immune microenvironment: implications for combination therapies.Frontiers in oncology · 2026Review
- PD-1/PD-L1 blockade in HIV-associated advanced lung cancer: from mechanisms to clinical practice.Frontiers in immunology · 2026Review
- Free-floating patient-derived organotypic tumor spheroids (PDOTS) from non-small cell lung cancer (NSCLC) tumors: a versatile tool for personalized testing of chemotherapeutic drugs.Research in pharmaceutical sciences · 2025Article
- HBO1 determines epithelial-mesenchymal transition and promotes immunotherapy resistance in ovarian cancer cells.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Orlistat facilitates immunotherapy via AKT-FOXO3a-FOXM1-mediated PD-L1 suppression.Journal for immunotherapy of cancer · 2025Article
- Genome-wide CRISPR screening identifies PHF8 as an effective therapeutic target for KRAS- or BRAF-mutant colorectal cancers.Journal of experimental & clinical cancer research : CR · 2025Article
- Article
- Role of PD-1/PD-L1 signaling axis in oncogenesis and its targeting by bioactive natural compounds for cancer immunotherapy.Military Medical Research · 2024Review
54 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) have improved the survival of patients with non-small cell lung cancer (NSCLC). Still, many patients do not respond to these inhibitors. PD-L1 (CD274) expression, one of the factors that influences the efficacy of immune checkpoint inhibitors, is dynamic. Here, we studied the regulation of PD-L1 expression in NSCLC without targetable genetic alterations in EGFR, ALK, BRAF, ROS1, MET, ERBB2 and RET. Analysis of RNA sequencing data from these NSCLCs revealed that inferred IFNγ, EGFR and MAPK signaling correlated with CD274 gene expression in lung adenocarcinoma. In a representative lung adenocarcinoma cell line panel, stimulation with EGF or IFNγ increased CD274 mRNA and PD-L1 protein and membrane levels, which were further enhanced by combining EGF and IFNγ. Similarly, tumor cell PD-L1 membrane levels increased after coculture with activated peripheral blood mononuclear cells. Inhibition of the MAPK pathway, using EGFR inhibitors cetuximab and erlotinib or the MEK 1 and 2 inhibitor selumetinib, prevented EGF- and IFNγ-induced CD274 mRNA and PD-L1 protein and membrane upregulation, but had no effect on IFNγ-induced MHC-I upregulation. Interestingly, although IFNγ increases transcriptional activity of CD274, MAPK signaling also increased stabilization of CD274 mRNA. In conclusion, MAPK pathway activity plays a key role in EGF- and IFNγ-induced PD-L1 expression in lung adenocarcinoma without targetable genetic alterations and may present a target to improve the efficacy of immunotherapy. © 2019 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
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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.