Tumor‐associated N1 and N2 neutrophils predict prognosis in patients with resected pancreatic ductal adenocarcinoma: A preliminary study

Dear Editor, Pancreatic ductal adenocarcinoma (PDAC) has been widely considered as one of the most lethal malignancies with a 5-year overall survival (OS) rate of only 11%.1 Lots of efforts have beendevoted into its early diagnosis, treatment strategies, and pathogenesis, etc. PDAC is characterized as excessive desmoplastic tumor with abundant immune cells infiltration, mainly including macrophages, T cells, immature myeloid cells, and neutrophils. Neutrophils are the most abundant white blood cells in blood and have been regarded as a homogeneous group in the past, which belongs to innate immune system and participates in defensing against pathogens. Recently, accumulating evidences determined that neutrophils had an important role in PDAC and accounted for a substantial proportion of tumor-infiltrating immune and inflammatory cells. Jiang et al.2 found that increased neutrophil infiltration was discovered as a central and prominent affected feature, which occurred in the liver, lung, and stomach at the PanIN stage. Importantly, serum leukotriene B4 (LTB4), derived from neutrophils, was validated for the early detection of PDAC. Considering its prognostic role, Ino et al.3 described relationships between prognosis and infiltrating immune cells in a cohort enrolled 212 PDAC patients who received radical surgical resection and found that tumor-infiltrating neutrophils were positively correlated with macrophages and regulatory T cells infiltrations and closely associated with shorter OS and disease-free survival (FS). This indicated that high tumor-infiltrating neutrophils always present boost immunosuppressive microenvironment and contribute to poor survival. Apart from tumor-infiltrating neutrophils, higher circulating neutrophils have also been found a negative association with outcomes. In our previous report, we noted that circulating neutrophil counts, whether 3 days within preoperation or 1 day after operation, were associated with shorter recurrence-FS (RFS) but

[1]  Jinyan Huang,et al.  Single-cell RNA-seq analysis reveals BHLHE40-driven pro-tumour neutrophils with hyperactivated glycolysis in pancreatic tumour microenvironment , 2022, Gut.

[2]  J. Ji,et al.  Modeling of cancer-related body-wide effects identifies LTB4 as a diagnostic biomarker for pancreatic cancer , 2022, EBioMedicine.

[3]  A. Jemal,et al.  Cancer statistics, 2022 , 2022, CA: a cancer journal for clinicians.

[4]  Shih-Ying Wu,et al.  Nicotine promotes breast cancer metastasis by stimulating N2 neutrophils and generating pre-metastatic niche in lung , 2021, Nature Communications.

[5]  A. Mantovani,et al.  Neutrophil diversity and plasticity in tumour progression and therapy , 2020, Nature Reviews Cancer.

[6]  Wenchuan Wu,et al.  Independent effect of postoperative neutrophil-to-lymphocyte ratio on the survival of pancreatic ductal adenocarcinoma with open distal pancreatosplenectomy and its nomogram-based prediction , 2019, Journal of Cancer.

[7]  Wenchuan Wu,et al.  Cell-intrinsic PD-1 Promotes Proliferation in Pancreatic Cancer by Targeting CYR61/CTGF via the Hippo Pathway. , 2019, Cancer letters.

[8]  Y. Kanai,et al.  Immune cell infiltration as an indicator of the immune microenvironment of pancreatic cancer , 2013, British Journal of Cancer.

[9]  L. Norton,et al.  Tumor entrained neutrophils inhibit seeding in the premetastatic lung. , 2011, Cancer cell.

[10]  A. M. Hicks,et al.  Transferable anticancer innate immunity in spontaneous regression/complete resistance mice , 2006, Proceedings of the National Academy of Sciences of the United States of America.