Unraveling the role of interferon-stimulated neutrophils: A promising biomarker for immunotherapy efficacy and prognosis in gastric adenocarcinoma.

• DOI: 10.1200/jco.2025.43.4_suppl.472
• Publication Date: 2025-01-27T14:37:03Z
• Authors: Hongda Pan; Fenglin Liu
• Keywords: Gastric adenocarcinoma

472 Background: Despite significant advancements in immunotherapy, the identification of effective predictive biomarkers for treatment response gastric adenocarcinoma (GAC) remains a critical challenge. Discovering such could enhance patient stratification and improve therapeutic outcomes. Methods: We conducted comprehensive analysis 18 specimens obtained from 10 GAC patients, both prior to following immunotherapy. Utilizing single-cell RNA sequencing, we compared cellular composition functional phenotypes these specimens, with particular emphasis on tumor-infiltrating immune cells previously uncharacterized neutrophil subclusters. Results: Our identified eight distinct subclusters, including Neu01_S100A12, Neu02_VEGF, Neu03_CCL3_CCL4, Neu04_IL1β, Neu05_CXCR4, Neu06_IFN-Stimulated, Neu07_Proliferative, Neu08_B-cell_related. Notably, presence IFN-Stimulated neutrophils was positively correlated efficacy immunotherapy GAC, finding that further validated through analyses public datasets in-house cohort studies employing multiplex immunohistochemistry. Additionally, served as prognostic indicators across multiple datasets. Investigations revealed engage communication other components within tumor microenvironment, CD8+ T cells, macrophages, B thereby promoting pro-inflammatory anti-tumor phenotype. Importantly, pan-cancer demonstrated consistent efficacy-predicting potential various cancer types. Conclusions: represent promising biomarker predicting prognosis GAC. findings offer novel insights into underlying mechanisms highlight avenues personalized strategies management