Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a malignancy with a poor prognosis and low survival rates. PDAC is characterized by a fibroinflammatory tumor microenvironment enriched by abundant fibroblasts and a variety of immune cells, contributing to its aggressiveness. Neutrophils are essential infiltrating immune cells in the PDAC microenvironment. Recent studies have identified several cellular mechanisms by which neutrophils are recruited to tumor lesion and promote tumorigenesis. This review summarizes the current understanding of the interplay between neutrophils, tumor cells, and other components in the PDAC tumor microenvironment. The prognosis and therapeutic implications of neutrophils in PDAC are also discussed.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with a five-year survival rate of 10% and is predicted to be the second leading cause of cancerrelated death by 2030 [1,2]
Another group found that a high CD15+ tumor-associated neutrophils (TANs) to CD8+ lymphocyte ratio in PDAC was associated with worse overall survival [30]
CXCR2 inhibitor treatment prolonged the survival of KPC mice and significantly protected from metastasis
Summary
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with a five-year survival rate of 10% and is predicted to be the second leading cause of cancerrelated death by 2030 [1,2]. Recent studies discovered an early homogeneous neutrophil progenitor subset in human bone marrow defined by surface markers CD71 and CD117 [4] These CD71+ neutrophils proliferate and expand in the blood and tumors from cancer patients. N1 neutrophils are characterized as CD101+ , CD177+ , CD170low , CD54+ , HLA-DR+ , CD86+ , and CD15high , whereas N2 neutrophils are CD170high , CD117+ , Lectin-like oxidized LDL receptor 1 (LOX1)+ , CD84+ , junctional adhesion molecule-like (JAML)+ , and PD-L1+ [15] This dichotomized classification of TANs may be overly simplified because, in some tumors, such as 3-MCA-induced primary sarcomas, TANs have a mixed phenotype between N1 and N2 [14,15]. We will discuss the clinical implications of neutrophils in PDAC
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