Granulocyte-Macrophage Colony-Stimulating Factor-Activated Neutrophils Express B7-H4 That Correlates with Gastric Cancer Progression and Poor Patient Survival

作者：Zhi‐guo Shan, Zong‐Bao Yan, Liu‐sheng Peng, Ping Cheng, Yong‐sheng Teng, Fangyuan Mao, Kun Fan, Yuan Zhuang, Yongliang Zhao · 发表于：Journal of Immunology Research · 年份：2021 · DOI：10.1155/2021/6613247 · 被引用次数：18 · 研究领域：Immune cells in cancer、Cancer Immunotherapy and Biomarkers、Cytokine Signaling Pathways and Interactions

Neutrophils are prominent components of gastric cancer (GC) tumors and exhibit distinct phenotypes in GC environment. However, the phenotype, regulation, and clinical relevance of neutrophils in human GC are presently unknown. Here, immunohistochemistry, real-time PCR, and flow cytometry analyses were performed to examine levels and phenotype of neutrophils in samples from 41 patients with GC, and also isolated, stimulated, and/or cultured neutrophils for in vitro regulation assays. Finally, we performed Kaplan-Meier plots for overall survival by using the log-rank test to evaluate the clinical relevance of neutrophils and their subsets. In our study, neutrophils in tumor tissues were significantly higher than those in nontumor tissues and were positively associated with tumor progression but negatively correlated with GC patient survival. Most intratumoral neutrophils showed an activated CD54+ phenotype and expressed high-level immunosuppressive molecule B7-H4. Tumor tissue culture supernatants from GC patients induced neutrophils to express CD54 and B7-H4 in both time-dependent and dose-dependent manners. Locally enriched CD54+ neutrophils and B7-H4+ neutrophils positively correlated with increased granulocyte-macrophage colony-stimulating factor (GM-CSF) detection ex vivo, and in vitro GM-CSF induced the expression of CD54 and B7-H4 on neutrophils in a time-dependent and dose-dependent manner. Moreover, GC tumor-derived GM-CSF activated neutrophils and induced neutrophil B...