Journal
CLINICAL IMMUNOLOGY
Volume 227, Issue -, Pages -Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2021.108753
Keywords
Gastric cancer; Neutrophils; B7-H3; Granulocyte-macrophage colony stimulating; factor
Categories
Funding
- National Natural Science Foundation of China [81902922, 81872016]
- Chongqing National Science Fund for Distinguished Young Scholars [cstc2019jcyjjqX0003]
- Science Innovation Capacity Promotion Project of Army Medical University [2019XQY03]
- National Key Research and Development Program of China [2016YFC1302200]
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In gastric cancer tumors, neutrophils expressing CD54 and B7-H3 are closely associated with changes in GM-CSF levels, activating through the JAK-STAT3 signaling pathway. B7-H3+ neutrophils may potentially serve as biomarkers in gastric cancer, increasing with tumor progression and predicting overall survival.
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 timedependent 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.
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