Neutrophils in pancreatic cancer: Potential therapeutic targets

Abstract

Pancreatic cancer is a digestive system malignancy and poses a high mortality worldwide. Traditionally, neutrophils have been thought to play a role in acute inflammation. In contrast, their importance during tumor diseases has been less well studied. Generally, neutrophils are recruited into the tumor microenvironment and exert inflammation and tumor-promoting effects. As an essential part of the tumor microenvironment, neutrophils play diverse roles in pancreatic cancer, such as angiogenesis, progression, metastasis and immunosuppression. Additionally, neutrophils can be a new potential therapeutic target in cancer. Inhibitors of cytokines, chemokines and neutrophil extracellular traps can exert antitumor effects. In this review, we describe the role of neutrophils in the development and progression of pancreatic cancer, discuss their potential as therapeutic targets, and aim to provide ideas for improving the prognosis of patients with this malignant tumor disease.

Clinical significance of FBXO43 in hepatocellular carcinoma and its impact on tumor cell proliferation, migration and invasion

“…Besides, there have been reports indicating that Tregs inhibits the cytotoxicity of CD8 + T cells, resulting in a negative outcome for HCC ( Moghaddam et al, 2022 ; Zheng et al, 2017 ). An increasing number of studies have shown that neutrophil not only play a crucial role in creating an immunosuppressive environment that supports tumor development, but also act as a driving force in tumor progression ( Jiang et al, 2022 ; Shaul & Fridlender, 2019 ). It also plays an important driving role in HCC ( Geh et al, 2022 ).…”

Trends in the burden of pancreatic cancer due to high fasting plasma glucose in China, 1990-2019, and projections until 2029

“…The longitudinal age curve, on the contrary, denotes the cohort-and period-adjusted longitudinal age-speci c rates. Finally, period (cohort) RRs are period (or cohort) relative risk adjusted for age and nonlinear cohort (or period) effect in a period (or cohort) versus the reference period (or cohort) [12]. In the age-period-cohort analysis, the number of deaths and the population were arranged into consecutive 5-year periods from 1990 to 2019 and successive 5-year age groups from 25 to 29 and from 90 to 94.…”

Unveiling the immunosuppressive landscape of pancreatic ductal adenocarcinoma: implications for innovative immunotherapy strategies

“…Neutrophils respond to low-dose IFN-β and transform into anti-tumor subsets that secrete CCL3, CXCL9, and other chemokines, promoting immunity by recruiting CD8 + T cells. They also increase TNF-α and ROS expression to amplify cytotoxicity ( 61 ). Furthermore, antineoplastic neutrophils mediate the release of IL-1 and hepatocyte growth factor (HGF) to exert antibacterial activity and increase the production of iNOS to kill tumor cells, respectively ( 61 ).…”

“…They also increase TNF-α and ROS expression to amplify cytotoxicity ( 61 ). Furthermore, antineoplastic neutrophils mediate the release of IL-1 and hepatocyte growth factor (HGF) to exert antibacterial activity and increase the production of iNOS to kill tumor cells, respectively ( 61 ). TGF-β induced TANs differentiation of tumor subpopulations ( 62 ).…”

“…Targeted therapy combined with other regimens may improve tolerance and therapeutic effect. There are two main solutions to suppress NETs: inhibiting peptide arginine deiminase 4 (PADI4) to reduce its formation or exploiting DNase and chloroquine to destroy its structure ( 61 ). Thrombomodulin inhibits the transformation of epithelial cells into mesenchymal cells induced by NETs ( 70 ).…”