Neutrophils in primary gastric tumors are correlated with neutrophil infiltration in tumor-draining lymph nodes and the systemic inflammatory response

Background: Tumor-Associated Neutrophils (TANs) may be able to induce lymphangiogenesis and angiogenesis, although the detailed roles of TANs remain unclear. The Neutrophil-Lymphocyte Ratio (NLR) is an inflammation-based prognostic factor for gastric cancer. This study aimed to investigate the distribution of CD15(+)neutrophils in the primary tumor and Tumor-Draining Lymph Nodes (TDLNs), and to examine the association of TANs with the clinicopathological features (including NLR) of patients with gastric cancer. Results: Immunohistochemical staining showed that the median number of CD15(+)TANs was 18 and 24 per high-power field (HPF) in primary tumors and TDLNs, respectively. Patients were divided into high and low infiltration groups based on the median number. A high number of infiltrating CD15(+)TANs in the primary tumors and in the TDLNs were associated with depth of invasion and lymph node metastasis. Kaplan-Meier analysis revealed that a poor overall survival was associated with high numbers of CD15(+)TANs, and the multivariate analyses revealed that a high number of CD15(+)TANs in the TDLNs was an independent prognostic factor. The numbers of CD15(+)TANs in the primary tumors and TDLNs showed weak positive correlation. The number of CD15(+)TANs in the primary tumors was positively correlated with the preoperative NLR, (P=0.001, R=0327) and immunohistochemical staining revealed that C-X-C motif chemokine receptor 2 (CXCR2) (+)neutrophils might be the origin of the CD15(+)TANs. Flow cytometry analysis indicated that infiltrating neutrophils increased in the tumor and TDLN compared to non-cancerous tissue. Neutrophils treated with cancer supernatant upregulated TWIST and IL-6 genes in vitro. Conclusion: Our findings suggested that local infiltration of CD15(+)TANs may be correlated with inflammation in TDLNs and systemic response to cause metastasis in gastric carcinoma.