ArticleGastroenterology2023
Key Genetic Determinants Driving Esophageal Squamous Cell Carcinoma Initiation and Immune Evasion.
Article in Gastroenterology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 67 citations in OpenAlex.
- Identification of STAT1 as a biomarker for lymph node metastasis in esophageal squamous cell carcinoma.Journal of molecular histology · 2026Article
- CRACD loss drives hypoxia-induced immune escape in gastric cancer.Nature communications · 2026Article
- Targeting the Notch signaling pathway in digestive system cancers: from bench to bedside.Cancer cell international · 2026Review
- Risk model based on adenylate uridylate (AU)-rich elements genes for assessing esophageal cancer prognosis and immune landscape.Journal of thoracic disease · 2026Article
- EZH2 as regulator of stemness signature and driver of esophageal squamous cell carcinomas.Scientific reports · 2026Article
- Spatiotemporal Transcriptomic Dissection Uncovers Age-Dependent Deceleration of Esophageal Cell Differentiation.bioRxiv : the preprint server for biology · 2026Article
- The Impact of Targeting TRAF2 and NCK-Interacting Protein Kinase on Antitumor Effect and Tumor Immune Environment in c-MYC-High SCLC.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026Article
- ADAMDEC1-driven CCL2-CCR2-PD-1 axis in esophageal squamous cell carcinoma: a dual threat of O-GlcNAcylation and mCellular oncology (Dordrecht, Netherlands) · 2026Article
- The advancements in organoids: Potential and challenges in researching the esophagus and esophageal squamous cell carcinoma.Genes & diseases · 2026Review
- MicroRNAs in Esophageal Cancer: Implications for Diagnosis, Progression, Prognosis and Chemoresistance.International journal of molecular sciences · 2026Review
- An Immune-privileged niche mediates immunotherapy resistance in esophageal carcinoma.Journal for immunotherapy of cancer · 2026Article
- Targeting notch signaling pathway in esophageal cancer: from molecular insights to therapies.Oncology reviews · 2026Review
- Single-Cell Lineage Trajectory Defines Cyclin-Dependent Kinase Inhibitor-Sensitive Cells-of-Origin in Esophageal Squamous Cell Carcinoma.Gastro hep advances · 2026Article
- Construction of circadian clock signature for tumor microenvironment in predicting survival of esophageal squamous cell carcinoma.Frontiers in immunology · 2026Article
- Ectopic CD11c Drives SMAD3-Mediated Aberrant Antigen Presentation and Epithelial-Mesenchymal Transition in Esophageal Squamous Cell Carcinoma.Cancer communications (London, England) · 2026Article
- The construction of CD8+ T cell-associated molecular subtypes in esophageal squamous cell carcinoma reveals tumor heterogeneity, tumor microenvironment, and immunotherapy.Frontiers in immunology · 2026Article
- Organoids glimpse: the nexus for diverse tumor heterogeneity.Frontiers in cell and developmental biology · 2026Review
- Deciphering precursor cell dynamics in esophageal preneoplasia via genetic barcoding and single-cell transcriptomics.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Next-generation sequencing identifies potential mechanisms of primary resistance to trastuzumab-containing therapies in HER2-positive gastric cancer: Analysis based on real-world data and online databases.Human vaccines & immunotherapeutics · 2025Article
- Single-cell insights into tumor microenvironment heterogeneity and plasticity: transforming precision therapy in gastrointestinal cancers.Journal of experimental & clinical cancer research : CR · 2025Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsDespite recent progress in identifying aberrant genetic and epigenetic alterations in esophageal squamous cell carcinoma (ESCC), the mechanism of ESCC initiation remains unknown.
methodsUsing CRISPR/Cas 9-based genetic ablation, we targeted 9 genes (TP53, CDKN2A, NOTCH1, NOTCH3, KMT2D, KMT2C, FAT1, FAT4, and AJUBA) in murine esophageal organoids. Transcriptomic phenotypes of organoids and chemokine released by organoids were analyzed by single-cell RNA sequencing. Tumorigenicity and immune evasion of organoids were monitored by allograft transplantation. Human ESCC single-cell RNA sequencing data sets were analyzed to classify patients and find subsets relevant to organoid models and immune evasion.
resultsWe established 32 genetically engineered esophageal organoids and identified key genetic determinants that drive ESCC initiation. A single-cell transcriptomic analysis uncovered that Trp53, Cdkn2a, and Notch1 (PCN) triple-knockout induces neoplastic features of ESCC by generating cell lineage heterogeneity and high cell plasticity. PCN knockout also generates an immunosuppressive niche enriched with exhausted T cells and M2 macrophages via the CCL2-CCR2 axis. Mechanistically, CDKN2A inactivation transactivates CCL2 via nuclear factor-κB. Moreover, comparative single-cell transcriptomic analyses stratified patients with ESCC and identified a specific subtype recapitulating the PCN-type ESCC signatures, including the high expression of CCL2 and CD274/PD-L1.
conclusionsOur study unveils that loss of TP53, CDKN2A, and NOTCH1 induces esophageal neoplasia and immune evasion for ESCC initiation and proposes the CCL2 blockade as a viable option for targeting PCN-type ESCC.
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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.