Frontiers in Immunology (May 2021)

Neutrophil Extracellular Traps and Macrophage Extracellular Traps Predict Postoperative Recurrence in Resectable Nonfunctional Pancreatic Neuroendocrine Tumors

  • Shuai-Shuai Xu,
  • Shuai-Shuai Xu,
  • Shuai-Shuai Xu,
  • Shuai-Shuai Xu,
  • Hao Li,
  • Hao Li,
  • Hao Li,
  • Hao Li,
  • Tian-Jiao Li,
  • Tian-Jiao Li,
  • Tian-Jiao Li,
  • Tian-Jiao Li,
  • Shuo Li,
  • Shuo Li,
  • Shuo Li,
  • Shuo Li,
  • Huan-Yu Xia,
  • Huan-Yu Xia,
  • Huan-Yu Xia,
  • Huan-Yu Xia,
  • Jiang Long,
  • Jiang Long,
  • Jiang Long,
  • Jiang Long,
  • Chun-Tao Wu,
  • Chun-Tao Wu,
  • Chun-Tao Wu,
  • Chun-Tao Wu,
  • Wen-Quan Wang,
  • Wen-Quan Wang,
  • Wen-Quan Wang,
  • Wen-Quan Wang,
  • Wu-Hu Zhang,
  • Wu-Hu Zhang,
  • Wu-Hu Zhang,
  • Wu-Hu Zhang,
  • He-Li Gao,
  • He-Li Gao,
  • He-Li Gao,
  • He-Li Gao,
  • Xuan Han,
  • Xuan Han,
  • Xuan Han,
  • Xuan Han,
  • Long-Yun Ye,
  • Long-Yun Ye,
  • Long-Yun Ye,
  • Long-Yun Ye,
  • Xuan Lin,
  • Xuan Lin,
  • Xuan Lin,
  • Xuan Lin,
  • Hua-Xiang Xu,
  • Hua-Xiang Xu,
  • Hua-Xiang Xu,
  • Hua-Xiang Xu,
  • Xian-Jun Yu,
  • Xian-Jun Yu,
  • Xian-Jun Yu,
  • Xian-Jun Yu,
  • Liang Liu,
  • Liang Liu,
  • Liang Liu,
  • Liang Liu

DOI
https://doi.org/10.3389/fimmu.2021.577517
Journal volume & issue
Vol. 12

Abstract

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BackgroundExtracellular traps (ETs) and tumor-infiltrating immune cells can contribute to disease progression. The clinical significance of tumor-infiltrating neutrophils and macrophages and related extracellular traps in pancreatic neuroendocrine tumors (pNETs) has not been fully elucidated. This study aimed to explore the prognostic value of tumor infiltration and ET formation by neutrophils and macrophages in pNETs.MethodsA total of 135 patients with radical resection of nonfunctional pNETs were analyzed retrospectively. Immunohistochemistry and immunofluorescence were utilized to stain tumor tissue sections. The recurrence-free survival (RFS) of subgroups determined by Kaplan-Meier analysis was compared with the log-rank test. Univariate and multivariate Cox regression analyses were used to identify independent prognostic factors. A nomogram was established to predict 3-year RFS.ResultsPatients with high tumor-infiltrating neutrophils or macrophages or positive expression of neutrophils ETs or macrophage ETs displayed worse RFS (all p<0.05). Moreover, univariate and multivariate Cox regression analyses showed that neutrophil and macrophage infiltration and ETs were independent prognostic factors for RFS (all p<0.05). A combined parameter including WHO grade, TNM stage, tumor-infiltrating neutrophils and macrophages, and neutrophil and macrophage ETs had the highest C-index (0.866) and lowest Akaike information criteria (326.557). The calibration plot of nomogram composed of the combined parameter exhibited excellent prognostic values for 3-year RFS.ConclusionsInfiltration and ETs by neutrophils and macrophages can be used as biological indicators of patient prognosis, suggesting the treatment potential for targeting those in nonfunctional pNETs.

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