ArticleBMC gastroenterology2025
Unveiling the heterogeneity and immunotherapy potency of tumor-associated neutrophils in the tumor microenvironment of gastric cancer.
Article in BMC gastroenterology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Emerging roles of Notch signaling in the tumor microenvironment of digestive system cancers.Frontiers in molecular biosciences · 2026Review
- Therapeutic vulnerability shaped by the microenvironment: multi-omics and AI biomarkers for precision surgical planning in gastrointestinal tumors.Frontiers in cell and developmental biology · 2026Article
- Hematological biomarkers for predicting pathologic response to neoadjuvant immunochemotherapy and cycle optimization in locally advanced gastric cancer.Frontiers in immunology · 2026Article
- Integrative Analysis of Neutrophil-Associated Genes Reveals Prognostic Significance and Immune Microenvironment Modulation in Cervical Cancer.Biomedicines · 2025Article
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Authors and funding
5 authors.
Funding
Abstract
backgroundThe differentiation characteristics of neutrophils within the gastric cancer (GC) tumor microenvironment (TME) and their interactions with malignant gastric epithelial cells require further investigation. Furthermore, the therapeutic potential of tumor-associated neutrophils (TANs) in immunotherapy remains inadequately explored.
methodsWe integrated two single-cell transcriptome datasets comprising 12 samples, including gastric primary tumors, non-tumor tissues, and metastatic tumors, to profile the epithelial cells and TANs atlas within the TME and examine their interaction modules. In addition, these data were integrated with the bulk transcriptomic including the Cancer Genome Atlas - Stomach Adenocarcinoma (TCGA-STAD) and Asian Cancer Research Group (ACRG) datasets to analyze the expression levels of neutrophil-associated genes across the tumor-associated neutrophil subsets.
resultsWe analyzed 3,118 gastric epithelial cells and 2,365 TANs from all samples. Epithelial cells were classified into ten subclusters, while TANs were grouped into five subclusters. In gastric primary tumors, epithelial cell subtypes included primarily MUC16 + and stem-like populations. In metastatic tumors, the epithelial cell subset with high CXCL5 expression was a characteristic subtype. TANs mainly interacted with epithelial cells via the LGALS9-CD45 and CD46-JAG1 pathways. And RGS2 was highly expressed in N4, a tumor-associated neutrophils subcluster characterized by high MMP9 expression, highlighting its potential as an immunotherapy target.
conclusionTANs exhibit robust interactions with gastric malignant epithelial cell subsets. Furthermore, RGS2, which is highly expressed in N4, could serve as a promising target for immunotherapy.
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