ArticleJournal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer2018
Immune Marker Profiling and Programmed Death Ligand 1 Expression Across NSCLC Mutations.
Article in Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 4 of them syntheses that pooled it.
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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.
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Who cites it
84 citing papers in PubMed, 4 syntheses or guidelines pooled it, 110 citations in OpenAlex.
- Inhibitors of PD-1 in Non-Small Cell Lung Cancer: A Meta-Analysis of Clinical and Molecular Features.Frontiers in immunology · 2022Pooled it
- Efficacy of Atezolizumab for Advanced Non-Small Cell Lung Cancer Based on Clinical and Molecular Features: A Meta-Analysis.Frontiers in immunology · 2022Pooled it
- The Efficacy of Immune Checkpoint Inhibitors vs. Chemotherapy for KRAS-Mutant or EGFR-Mutant Non-Small-Cell Lung Cancers: A Meta-Analysis Based on Randomized Controlled Trials.Disease markers · 2022Pooled it
- Molecular heterogeneity of anti-PD-1/PD-L1 immunotherapy efficacy is correlated with tumor immune microenvironment in East Asian patients with non-small cell lung cancer.Cancer biology & medicine · 2020Pooled it
- Neoadjuvant sintilimab and chemotherapy in patients with potentially resectable esophageal squamous cell carcinoma (KEEP-G 03): an open-label, single-arm, phase 2 trial.Journal for immunotherapy of cancer · 2023Trial
- Spatial single-cell proteotyping reveals immunotherapy-resistant features within the complex tumor microenvironment of metastatic NSCLC.The Journal of clinical investigation · 2026Article
- Revisiting Biomarker-Guided Therapy in EGFR-Mutant Non-Small Cell Lung Cancer with High PD-L1 Expression.International journal of molecular sciences · 2026Review
- Efficacy of Adding Immune Checkpoint Inhibition to Chemotherapy, With or Without VEGF Inhibition, in Patients With AdvancedJTO clinical and research reports · 2026Article
- EGFR activation disrupts immunotherapy response via SHP2-mediated suppression of tumor-intrinsic response to IFN-γ.The Journal of clinical investigation · 2026Article
- A novel mouse cell line model reveals the tumor intrinsic and immune characteristics of EGFR-mutant lung cancer.Theranostics · 2026Article
- PD-1/PD-L1 blockade in HIV-associated advanced lung cancer: from mechanisms to clinical practice.Frontiers in immunology · 2026Review
- Efficacy and mechanisms of immune checkpoint inhibitors in late-stage EGFR-mutated non-small cell lung cancer following targeted therapy resistance.Frontiers in immunology · 2026Review
- Machine learning identifies TIME subtypes linking EGFR mutations and immune states in lung adenocarcinoma.NPJ digital medicine · 2025Article
- The paradoxical prognostic effects of T-cell-derived circulating DNA in EGFR-mutated advanced non-small-cell lung cancer involve the crosstalk between heme biosynthesis and immune microenvironment.Scientific reports · 2025Article
- EGFR: New Insights on Its Activation and Mutation in Tumor and Tumor Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Novel therapeutic strategies for non-small cell lung cancer: Combination therapies with immune checkpoint inhibitors (Review).Oncology letters · 2025Review
- The correlation of HLA-A in Thai EGFR-mutated advanced non-small cell lung cancer, outcome, and tumor microenvironment.Scientific reports · 2025Article
- Recent Advances in the Use ofPharmaceutics · 2025Review
- Adjuvant pembrolizumab therapy for completely resected stage I lung adenocarcinoma with micropapillary or solid histological subtypes: a single-center, single-arm, phase 2 trial.EClinicalMedicine · 2025Article
- Pharmacological effects of osimertinib on a chicken chorioallantoic membrane xenograft model with the EGFR exon-19-deleted advanced NSCLC mutation.FEBS open bio · 2025Article
24 more citing papers are in PubMed but not listed here.
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 3 institutions in 2 countries.
Funding
Abstract
introductionProgrammed death 1/programmed death ligand 1 (PD-L1) axis inhibitors have been proven effective, especially in patients with tumors expressing PD-L1. Their clinical efficacy in patients with EGFR-activating mutations is still unclear, whereas KRAS mutations seem to be associated with good response.
methodsWe used multiplexed quantitative immunofluorescence to investigate PD-L1 expression and to characterize tumor infiltrating lymphocyte (TIL) populations and their activation status in more than 150 NSCLC patients with known mutation status.
resultsPD-L1 expression was significantly lower in EGFR-mutant compared to KRAS-mutant, and EGFR/KRAS wild-type (WT) tumors. KRAS mutant tumors were more inflamed with higher CD4+, CD8+ and CD20+ TILs. Subgroup analysis by TIL activation status revealed that EGFR mutants had a high frequency of inactive TILs even though lymphocytes were present in the tumor microenvironment. In contrast, in KRAS mutants, when TILs were present they were almost always active. Additionally, we found differences between EGFR mutation sites in CD8+ expression and the TIL activation profile. Finally, activated EGFR correlated with increased PD-L1 expression in EGFR mutants but not in EGFR WT, whereas TIL activation was associated with higher PD-L1 only in EGFR/KRAS WT.
conclusionsOur findings show the unique immune profile of EGFR-mutant tumors. The high frequency of inactive TILs could explain the low immunotherapy response rates in these patients, whereas PD-L1 as a predictive biomarker may reflect the constitutive oncogenic signaling rather than immune signaling, which would be associated with high PD-L1 levels and TILs activation.
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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.