ArticleJournal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer2021
Characterization of the Immune Landscape of EGFR-Mutant NSCLC Identifies CD73/Adenosine Pathway as a Potential Therapeutic Target.
Article in Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 3 of them syntheses that pooled it.
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Who cites it
81 citing papers in PubMed, 3 syntheses or guidelines pooled it, 124 citations in OpenAlex.
- Comparison of treatment regimens for unresectable stage III epidermal growth factor receptor ( EGFR ) mutant non-small cell lung cancer.Chinese medical journal · 2025Pooled it
- 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
- Trial
- Neoadjuvant Durvalumab Alone or Combined with Novel Immuno-Oncology Agents in Resectable Lung Cancer: The Phase II NeoCOAST Platform Trial.Cancer discovery · 2023Trial
- Tumor heterogeneity: development, mechanisms, and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- Regulatory B-cell states in NSCLC immunotherapy resistance: mechanisms, spatial context and translational implications.Cancer immunology, immunotherapy : CII · 2026Review
- Understanding immune checkpoint inhibitor efficacy through spatial decoding of the lung cancer tumor immune microenvironment.The Journal of clinical investigation · 2026Article
- Spatial single-cell proteotyping reveals immunotherapy-resistant features within the complex tumor microenvironment of metastatic NSCLC.The Journal of clinical investigation · 2026Article
- Unraveling the nexus: Tumor mutational burden, PD-L1 expression, and oncogenic alterations in non-small cell lung cancer cytology specimens.Cancer cytopathology · 2026Article
- USP5-mediated CD73 deubiquitination drives osimertinib resistance via PI3K/AKT and glycolysis activation in LUAD.iScience · 2026Article
- Immunotherapy for patients with EGFR-TKI-resistant non-small-cell lung cancer: Potential mechanisms, efficacy predictors, and therapeutic integration.Chinese medical journal pulmonary and critical care medicine · 2026Review
- Blood Based Biomarkers for Predicting Treatment Response to Immune Checkpoint Inhibitors After EGFR-TKI Resistance in Non-Small Cell Lung Cancer.Thoracic cancer · 2026Article
- Tumor Cells as Architects of Immune Refractoriness: Dismantling Intrinsic Programs of Tumor Cells for Clinical Translation.Immune network · 2026Review
- Profiling of Extracellular Vesicles of Non-Small Cell Lung Cancer Reveals Proteins Associated With Osimertinib Resistance.Journal of extracellular vesicles · 2026Article
- CD39+CD8+ T cell infiltration is associated with clinical outcomes of subsequent immunotherapy in advanced EGFR-mutant non-small cell lung cancer.Therapeutic advances in medical oncology · 2026Article
- CD73 expression as a resistance mechanism in advancedFrontiers in oncology · 2026Article
- Mitochondrial niches of residual disease in EGFR-mutant NSCLC: immune-constrained persistence and therapeutic interception.Frontiers in immunology · 2026Review
- The Activity of EGFR CAR NK and CAR T Cells against EGFR Inhibitor-Resistant NSCLC and Drug-Tolerant Persister Cells.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- CD24 is a promising immunotherapeutic target for enhancing efficacy of third-generation EGFR-TKIs on EGFR-mutated lung cancer.Cancer communications (London, England) · 2025Article
21 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
39 authors at 3 institutions in 1 country.
Funding
Abstract
introductionLung adenocarcinomas harboring EGFR mutations do not respond to immune checkpoint blockade therapy and their EGFR wildtype counterpart. The mechanisms underlying this lack of clinical response have been investigated but remain incompletely understood.
methodsWe analyzed three cohorts of resected lung adenocarcinomas (Profiling of Resistance Patterns of Oncogenic Signaling Pathways in Evaluation of Cancer of Thorax, Immune Genomic Profiling of NSCLC, and The Cancer Genome Atlas) and compared tumor immune microenvironment of EGFR-mutant tumors to EGFR wildtype tumors, to identify actionable regulators to target and potentially enhance the treatment response.
resultsEGFR-mutant NSCLC exhibited low programmed death-ligand 1, low tumor mutational burden, decreased number of cytotoxic T cells, and low T cell receptor clonality, consistent with an immune-inert phenotype, though T cell expansion ex vivo was preserved. In an analysis of 75 immune checkpoint genes, the top up-regulated genes in the EGFR-mutant tumors (NT5E and ADORA1) belonged to the CD73/adenosine pathway. Single-cell analysis revealed that the tumor cell population expressed CD73, both in the treatment-naive and resistant tumors. Using coculture systems with EGFR-mutant NSCLC cells, T regulatory cell proportion was decreased with CD73 knockdown. In an immune-competent mouse model of EGFR-mutant lung cancer, the CD73/adenosine pathway was markedly up-regulated and CD73 blockade significantly inhibited tumor growth.
conclusionsOur work revealed that EGFR-mutant NSCLC has an immune-inert phenotype. We identified the CD73/adenosine pathway as a potential therapeutic target for EGFR-mutant NSCLC.
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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.