ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
Neutrophils Recruited by NKX2-1 Suppression via Activation of CXCLs/CXCR2 Axis Promote Lung Adenocarcinoma Progression.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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
19 citing papers in PubMed.
- CCL3+ Neutrophil Signature Predicts Response to Neoadjuvant Toripalimab plus Chemotherapy in Patients with Hypopharyngeal Squamous Cell Carcinoma: A Phase II Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- Spatial Multiomics Analyses Reveal That Diabetes Promotes Pancreatic Cancer Progression by Stimulating Cholesterol-Induced Neutrophil Extracellular Trap Formation.Cancer research · 2026Article
- Mapping of Neutrophils in Cancers: Insights From Spatial Omics Technologies.European journal of immunology · 2026Review
- Unlocking Alveolar Regeneration: AT2 Stem Cells, Signaling Networks, and Therapeutic Frontiers.Stem cell reviews and reports · 2026Review
- Characterizing Chemokine Signaling Pathways and Hub Genes in Calcium Oxalate-Induced Kidney Stone Formation: Insights from Rodent Models.Biochemical genetics · 2026Article
- NAC and DNase I synergistically reduce NETs to attenuate severe acute pancreatitis via suppressing the NETs/NF-κB/CXCL3 pathway.Apoptosis : an international journal on programmed cell death · 2026Article
- CXCL1-CXCR2 axis inhibits melanogenesis through the suppression of the WNT/β-catenin pathway.Frontiers in immunology · 2026Article
- Candidate Biomarkers for Crohn's Disease: Hub Genes and Regulatory miRNAs Identified by Bioinformatics Analysis.Biochemistry research international · 2026Article
- CXCL2/CXCR2 pathway regulates CD169Frontiers in medicine · 2026Article
- Gene amplification in the premalignant stages of non-small cell lung cancer development.Frontiers in oncology · 2026Review
- BFAR Promotes Neutrophil Infiltration and Immunosuppressive Reprogramming through the PRP19-YBX1 Axis to Induce Immune Evasion in Gastric Cancer.Cancer immunology research · 2025Article
- Subtype-specific RNA sequencing using micro-dissection revealed extracellular matrix alterations as key factors in lung adenocarcinoma invasion.Translational lung cancer research · 2025Article
- [Molecular Mechanism of Neutrophils Driving the Progression of Lung Adenocarcinoma].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Review
- NKX2-1 Restricts the Growth and Metastasis of Lung Squamous Cell Carcinoma Through Transcriptive Suppression of AKR1B10.Journal of biochemical and molecular toxicology · 2025Article
- Exosomal CMTM4 Induces Immunosuppressive Macrophages to Promote Ovarian Cancer Progression and Attenuate Anti-PD-1 Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- NKX2-5/LHX1 and UHRF1 Establishing a Positive Feedback Regulatory Circuitry Drives Esophageal Squamous Cell Carcinoma through Epigenetic Dysregulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- CXCL2: a key player in the tumor microenvironment and inflammatory diseases.Cancer cell international · 2025Review
- Identification of the role of MED6 in the development and prognosis of lung adenocarcinoma based on multi-omics profiling.Journal of Cancer · 2025Article
- Neutrophils Recruited by NKX2-1 Suppression via Activation of CXCLs/CXCR2 Axis Promote Lung Adenocarcinoma Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
Corrections and comments
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Authors and funding
19 authors.
Funding
Abstract
NK2 Homeobox 1 (NKX2-1) is a well-characterized pathological marker that delineates lung adenocarcinoma (LUAD) progression. The advancement of LUAD is influenced by the immune tumor microenvironment through paracrine signaling. However, the involvement of NKX2-1 in modeling the tumor immune microenvironment is still unclear. Here, the downregulation of NKX2-1 is observed in high-grade LUAD. Meanwhile, single-cell RNA sequencing and Visium in situ capturing profiling revealed the recruitment and infiltration of neutrophils in orthotopic syngeneic tumors exhibiting strong cell-cell communication through the activation of CXCLs/CXCR2 signaling. The depletion of NKX2-1 triggered the expression and secretion of CXCL1, CXCL2, CXCL3, and CXCL5 in LUAD cells. Chemokine secretion is analyzed by chemokine array and validated by qRT-PCR. ATAC-seq revealed the restrictive regulation of NKX2-1 on the promoters of CXCL1, CXCL2, and CXCL5 genes. This phenomenon led to increased tumor growth, and conversely, tumor growth decreased when inhibited by the CXCR2 antagonist SB225002. This study unveils how NKX2-1 modulates the infiltration of tumor-promoting neutrophils by inhibiting CXCLs/CXCR2-dependent mechanisms. Hence, targeting CXCR2 in NKX2-1-low tumors is a potential antitumor therapy that may improve LUAD patient outcomes.
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