ArticleClinical and translational medicine2023
Cellular dynamics in tumour microenvironment along with lung cancer progression underscore spatial and evolutionary heterogeneity of neutrophil.
Article in Clinical and translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 28 citations in OpenAlex.
- Neutrophils in cancer.Nature reviews. Cancer · 2026Review
- Unveiling the role of spatial transcriptomics in the analysis of the tumor immune microenvironment (Review).International journal of molecular medicine · 2026Review
- Article
- Atherosclerotic Cardiovascular Disease and Cancer.Immunological reviews · 2026Review
- Mapping of Neutrophils in Cancers: Insights From Spatial Omics Technologies.European journal of immunology · 2026Review
- Amodiaquine Enhances Anti-Melanoma Efficacy of Attenuated Salmonella via Targeting Glutathione Reductase in Neutrophils.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Integrated single-cell and bulk RNA sequencing unravels neutrophil heterogeneity and validates SPP1 as a prognostic biomarker in cervical cancer.BMC cancer · 2026Article
- Spatiotemporal dynamics of tumor-associated neutrophils: bridging the gap between cancer progression and immunotherapy.Molecular cancer · 2026Review
- Synergistic Potential of Immune Checkpoint Inhibitor Combined with Neutrophil-Targeted Therapy in Cancer Immunotherapy.Research (Washington, D.C.) · 2026Review
- Tumor-associated neutrophils in lung adenocarcinoma: from mechanisms to therapeutic targeting.Frontiers in immunology · 2026Review
- Decoding the tumor immune microenvironment in lung squamous cell carcinoma: characteristics, regulatory mechanisms, and future directions in immunotherapy.Translational lung cancer research · 2025Review
- APOE-high myeloid cells are uniquely associated with metastatic intrathoracic lymph nodes obtained by EBUS-TBNA in primary lung cancer.NPJ precision oncology · 2025Article
- Radiogenomics of intrahepatic cholangiocarcinoma predicts immunochemotherapy response and identifies therapeutic target.Clinical and molecular hepatology · 2025Article
- Therapeutic potential of tumor-associated neutrophils: dual role and phenotypic plasticity.Signal transduction and targeted therapy · 2025Review
- Tumor‑associated neutrophils: Critical regulators in cancer progression and therapeutic resistance (Review).International journal of oncology · 2025Review
- Neutrophil heterogeneity and plasticity: unveiling the multifaceted roles in health and disease.MedComm · 2025Review
- Consumption of Endogenous Caspase-3 Activates Molecular Theranostic Nanoplatform against Inflammation-Induced Profibrotic Positive Feedback in Pulmonary Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Tumor-Activated Neutrophils Promote Lung Cancer Progression through the IL-8/PD-L1 Pathway.Current cancer drug targets · 2025Article
- The miR-941/FOXN4/TGF-β feedback loop induces N2 polarization of neutrophils and enhances tumor progression of lung adenocarcinoma.Frontiers in immunology · 2025Article
- Effect of neutrophils on tumor immunity and immunotherapy resistance with underlying mechanisms.Cancer communications (London, England) · 2025Review
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Authors and funding
15 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe cellular dynamics in the tumour microenvironment (TME) along with non-small cell lung cancer (NSCLC) progression remain unclear.
methodsMultiplex immunofluorescence test detecting 10 immune-related markers on 553 primary tumour (PT) samples of NSCLC was conducted and spatial information in TME was assessed by the StarDist depth learning model. The single-cell transcriptomic atlas of PT (n = 4) and paired tumour-draining lymph nodes (TDLNs) (n = 5 for tumour-invaded, n = 3 for tumour-free) microenvironment was profiled. Various bioinformatics analyses based on Gene Expression Omnibus, TCGA and Array-Express databases were also used to validate the discoveries.
resultsSpatial distances of CD4+ T cells-CD38+ T cells, CD4+ T cells-neutrophils and CD38+ T cells-neutrophils prolonged and they were replaced by CD163+ macrophages in PT along with tumour progression. Neutrophils showed unique stage and location-dependent prognostic effects. A high abundance of stromal neutrophils improved disease-free survival in the early-stage, whereas high intratumoural neutrophil infiltrates predicted poor prognosis in the mid-to-late-stage. Significant molecular and functional reprogramming in PT and TDLN microenvironments was observed. Diverse interaction networks mediated by neutrophils were found between positive and negative TDLNs. Five phenotypically and functionally heterogeneous subtypes of tumour-associated neutrophil (TAN) were further identified by pseudotime analysis, including TAN-0 with antigen-presenting function, TAN-1 with strong expression of interferon (IFN)-stimulated genes, the pro-tumour TAN-2 subcluster, the classical subset (TAN-3) and the pro-inflammatory subtype (TAN-4). Loss of IFN-stimulated signature and growing angiogenesis activity were discovered along the transitional trajectory. Eventually, a robust six neutrophil differentiation relevant genes-based model was established, showing that low-risk patients had longer overall survival time and may respond better to immunotherapy.
conclusionsThe cellular composition, spatial location, molecular and functional changes in PT and TDLN microenvironments along with NSCLC progression were deciphered, highlighting the immunoregulatory roles and evolutionary heterogeneity of TANs.
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