Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
Chongqing Key Research Laboratory for Drug Metabolism, Department of Pharmacology, Chongqing Medical University, Chongqing, China.
Clin Immunol. 2021 Jun;227:108753. doi: 10.1016/j.clim.2021.108753. Epub 2021 May 1.
Neutrophils are conspicuous components of gastric cancer (GC) tumors, increasing with tumor progression and poor patient survival. However, the phenotype, regulation and clinical relevance of neutrophils in human GC are presently unknown. Most intratumoral neutrophils showed an activated CD54 phenotype and expressed high level B7-H3. Tumor tissue culture supernatants from GC patients induced the expression of CD54 and B7-H3 on neutrophils in time-dependent and dose-dependent manners. Locally enriched CD54 neutrophils and B7-H3 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-H3 on neutrophils in both time-dependent and dose-dependent manners. Furthermore, GC tumor-derived GM-CSF activated neutrophils and induced neutrophil B7-H3 expression via JAK-STAT3 signaling pathway activation. Finally, intratumoral B7-H3 neutrophils increased with tumor progression and independently predicted reduced overall survival. Collectively, these results suggest B7-H3 neutrophils to be potential biomarkers in GC.
中性粒细胞是胃癌（GC）肿瘤中引人注目的组成部分，随着肿瘤的进展和患者生存状况的恶化而增加。然而，目前尚不清楚人类 GC 中中性粒细胞的表型、调节及其临床相关性。大多数肿瘤内中性粒细胞表现出活化的 CD54 表型，并表达高水平的 B7-H3。GC 患者的肿瘤组织培养上清液以时间和剂量依赖的方式诱导中性粒细胞表达 CD54 和 B7-H3。局部富含 CD54 的中性粒细胞和 B7-H3 阳性中性粒细胞与体外 GM-CSF 检测增加呈正相关；GM-CSF 在体外以时间和剂量依赖的方式诱导中性粒细胞表达 CD54 和 B7-H3。此外，GC 肿瘤衍生的 GM-CSF 通过 JAK-STAT3 信号通路激活中性粒细胞，并诱导中性粒细胞 B7-H3 的表达。最后，肿瘤内的 B7-H3 中性粒细胞随着肿瘤的进展而增加，并独立预测总生存期缩短。综上所述，这些结果表明 B7-H3 中性粒细胞是 GC 的潜在生物标志物。
